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OTHER  BOOKS   BY   DR.   FISCHER 

PUBLISHED   BT 

JOHN  WILEY  &  SONS,  Inc. 
432  Fourth  Avenue  New  York 


Oedema  and  Nephritis. 

A  Critical,  Experimental  and  Clinical  Study  of  the  Physiology 
and  Pathology  of  Water  Absorption  in  the  Living  Organism. 
Second  and  enlarged  edition.  695  pages,  6x9,  159  figures. 
Cloth,  $5.00  net  (21/-  net). 

The  Physiology  of  Alimentation. 

viii+  348  pages,  5 J  x  8,  30  figures.    Cloth,  $2.00  net. 
TRANSLATION 

Physical  Chemistry  in  the  Service  of  Medicine. 

Seven   Addresses   by    Dr.    Wolfgang   Pauli,    Professor  in   the 
Biological  Experiment  Station  in  Vienna.    Authorized  Trans- 
lation by  Dr.  Martin  H.  Fischer, 
ix  +  156  pages,  5  x  7|.     Cloth,  $1.25  net. 


Fats  and 
Fatty  Degeneration 

A  PHYSICO-CHEMICAL   STUDY  OF  EMULSIONS   AND 

THE  NORMAL  AND  ABNORMAL  DISTRIBUTION 

OF   FAT   IN   PROTOPLASM 


BY 

Dr.  martin   H.jFISCHER 

Eichherg  Professor  of  Physiology  in  me^niversity  of  Cincinnati 

AND 

Dr.  MARIAN   0.  HOOKER 

Instructor  in  Physiology  in  the  University  of  Cincinnati 


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FIRST  EDITION 


NEW  YORK 
JOHN   WILEY   &   SONS,   Inc, 

London:   CHAPMAN  &  HALL,  Limited 
1917 


•     Copyright.  1917,  bt 
MARTIN  H.  FISCHER 


Stanbopc  ipress 

H.GILSON    COMPANY 
BOSTON,  U.S.A. 


TO 


Houella  Cfiapin 


TEACHER.  COUNSELOR  AND  INSPIRATION  DAILY 
TO  A  THOUSAND  YOUTHS 


44447 


Breath  and  all  in  your  composition 
that  is  igneous  naturally  ascend, 
yet,  obedient  to  the  order  of  the 
whole,  they  retain  their  place  here 
in  the  compound.  The  earthy  and 
humid  parts,  on  the  other  hand, 
naturally  descend,  yet  are  raised 
and  retain  a  position  other  than 
their  natural  one.  Thus  the  ele- 
ments, wheresoever  placed,  obey 
the  law  of  the  whole,  waiting  till 
the  signal  be  given  for  their  dis- 
soluiion. 

Marcus  Aurelitjs. 


PREFACE. 

The  following  pages  give  in  collected  and  somewhat  am- 
plified form  the  results  of  experiments  which  have  not  pre- 
viously been  pubUshed  in  English,  excepting  in  abstract 
form  in  Science,  While  our  earUer  colloid-chemical  studies 
had  compelled  a  desultory  consideration  of  some  of  the 
problems  here  dealt  with,  this  detailed  study  of  the  qua^ 
tion  of  the  fat  in  the  cells  is  less  than  two  years  old.  ^^ 
turned  to  this  fat  problem  in  order  to  escape  from  older 
colloid-chemical  studies  on  oedema,  nephritis  and  alhed  sub- 
jects.^ In  this,  however,  we  were  early  doomed  to  disap- 
pointment. Without  intent  on  our  part,  the  conclusions  of 
these  newer  studies  dovetail  with  and  corroborate  the  older 
ones.  A  house  previously  looked  at  from  within  is  here 
seen  from  without  —  but  it  is  the  same  house. 

Martin  H.  Fischer. 
Marian  O.  Hooker. 

EiCHBERG  Laboratory  of  Physiology, 

University  of  Cincinnati. 

July  20,  1916. 


n 


*  See  "(Edema  and  Nephritis,"  second  edition.     John  Wiley  and  Sons, 
Inc.,  New  York,  1915. 

vii 


TABLE   OF   CONTENTS 

Page 

I.   The  Argument 3 

II.   On  the  Making  of  Emulsions 17 

1.  Introduction 19 

2.  Definition  and  Types  of  Emulsions 20 

3.  Experiments  on  Emulsions 21 

4.  On  the  Making  of  Emulsions . . . .' 25 

III.  On  the  Breaking  of  Emulsions 45 

1.  The  General  Rule 47 

2.  Illustrative  Experiments 47 

3.  Special  Considerations 53 

IV.  On  the  Normal  Fat  Content  of  Cells 55 

1.  The  General  Facts 57 

2.  Protoplasm  as  a  Fat-in-water  Type  of  Emulsion 60 

3.  Biological  Consequenqes 62 

V.  On  Fatty  Change  (Fatty  Infiltration  and  Fatty  Degen- 
eration)    65 

1.  Historical  Remarks 67 

2.  Fatty  Degeneration  in  Emulsions 69 

3.  Analogy  Between  the  Chemical  Conditions  Favoring  Fatty 
Degeneration  and  those  Producing  Coarsening  in  Emulsions  74 

4.  Tissue  Rigidity  and  Tissue  Softening 76 

5.  Further  Historical  Remarks     81 

VI.  The  Adipose  Tissues  and  the  Fatty  Secretions 87 

1.  The  Fatty  Tissues 89 

2.  The  Fatty  Secretions 91 

3.  Optical  Changes  Incident  to  Physical  Changes  in  Emulsions  96 

VII.   On  the  Natural  and  Artificial  Production  of  Milk 103 

1.  Introduction 105 

2.  The  Normal  (Biological)  Production  of  Milk 105 

3.  The  Artificial  Production  of  Milk 108 

VIII.   On  the  Mimicry  of  Mucoid  Secretion 115 

IX.   On  the  Mimicry  of  Some  Anatomical  Structures 119 

1.  Introduction 121 

2.  On  the  Mimicry  of  Certain  Anatomical  Structures 123 

3.  On  the  Protective  Coverings  of  Plants 138 

X.   Concluding  Paragraphs 143 

ix 


I.  THE  ARGUMENT. 


FATS  AND  FATTY  DEGENERATION 

I.   THE  ARGUMENT. 

1. 

This  introductory  chapter  follows  a  plan  which,  when 
used  in  a  previous  monograph,  elicited  favorable  comment. 
It  is  an  abstract  of  the  entire  volume,  designed  for  those 
who  have  not  time  to  read  the  whole  book.  The  experi- 
mental evidence  as  presented  in  these  first  pages  is  neces- 
sarily condensed;  where  it  proves  inadequate  to  carry  con- 
viction to  the  reader,  he  may  follow  the  extended  argument 
by  turning  to  pages  referred  to  in  the  course  of  the  abstract. 

II. 

The  importance  of  the  emulsions  and  of  a  knowledge  of 
their  properties  for  various  problems  in  physiology,  pathol- 
ogy and  technology,  is  emphasized.     (See  pages  19  to  20.) 

An  emulsion  is  by  definition  a  mixture  of  two  immiscible 
liquids  in  each  other,  as  of  oil  in  water.  Since  the  one  liquid 
is  subdivided  (dispersed)  in  the  other,  an  emulsion  is  one  of 
the  group  of  the  so-called  dispersed  systems.  Since  the 
properties  of  the  one  liquid  are  greatly  different  from  those 
of  the  second  in  an  emulsion,  we  note  that  it  is  made  up 
of  different  phases.  An  oil-in- water  emulsion  is,  in  other 
words,  diphasic.     (See  page  20.) 

To  the  pure  chemist,  an  emulsion  is  a  mechanical  mixture 
of  two  or  more  materials  and  so  to  him  they  are  all  alike, 
when  once  the  materials  to  make  up  an  emulsion  and  their 
amounts  are  settled  upon.  But  this  conclusion  is  wrong. 
From  the  same  quantities  of  oil  and  water,  for  example, 
two  entirely  different  types  of  emulsions  may  be  produced 
which  have  totally  different  properties.  There  may  be  made 
an  emulsion  of  the  oil  in  the  water  or  of  the  water  in  the  oil 
(See  pages  20  to  21.) 

3 


4  FATS  AND  FATTY   DEGENERATION 

Cottonseed  oil  and  water  are  chosen  as  the  materials  from 
which  to  produce  emulsions  in  order  to  study  the  laws  re- 
garding their  production,  their  maintenance,  their  destruc- 
tion and  their  general  properties. 

Oil  in  contact  with  pure  water  does  not  lead  spontane- 
ously to  the  formation  of  an  emulsion.  In  order  to  sub- 
divide the  one  material  in  the  second,  mechanical  mixers  of 
different  types  must  be  used.  The  construction  of  these 
and  their  relative  merits  are  discussed.    (See  pages  21  to  25.) 

The  amount  of  cottonseed  oil  ihat  may  be  permanently 
emulsified  in  pure  water  on  beating  the  two  together  is 
very  small,  not  exceeding  a  fraction  of  one  percent.  These 
emulsions  are,  however,  stabile.  The  oil  particles  in  such 
emulsions  are  rather  small,  their  dimensions  lying  within 
the  realm  of  the  colloids.  These  low  concentrations  of  oil 
in  water,  therefore,  really  represent  colloid  suspensions  of 
oil  in  water  and  possess  not  only  the  stability  character- 
istics of  such  systems,  but  also  their  well  known  ^^satura- 
tion limit.''     (See  pages  25  to  26.) 

The  term  ^'emulsion  "  is  ordinarily  used  to  cover  the  sub- 
division of  one  fluid  in  a  second  m  amounts  exceeding  these 
low  values.  The  mixture  must,  moreover,  show  a  fair  degree 
of  stability;  in  other  words,  the  two  liquids  constituting 
the  dispersoid  must  not  separate  in  the  course  of  weeks, 
months  or  years.  A  temporary  subdivision  of  any  quan- 
tity of  oil  in  a  given  volume  of  water,  or  the  converse,  can, 
of  course,  be  obtained  by  merely  beating  the  two  together. 
The  problem  of  emulsification,  therefore,  really  resolves 
into  two  parts:  first,  that  of  the  question  of  how  an  emul- 
sion may  be  produced;  and  second,  that  of  how,  once  the 
subdivision  of  the  oil  in  the  water  has  been  accomplished, 
this  subdivision  may  be  or  is  stabilized.  The  two  problems 
have  not  been  kept  apart  as  they  should  be.  (See  pages  26 
to  27.) 

Contrary  to  the  general  belief  of  different  workers  who 
have  each  tried  to  discover  some  one  element  to  be  respon- 
sible for  this  stabilization,  a  group  of  different  factors  evi- 


THE  ARGUMENT  5 

dently  plays  a  role,  the  relative  importance  of  each  factor 
varying  not  only  in  different  emulsions,  but  in  the  same 
emulsion  under  different  circumstances. 

It  is  generally  held  that  the  formation  and  the  mainten- 
ance of  an  emulsion  depend  upon  the  slight  surface  tension 
of  the  dispersing  medium,  and  its  high  viscosity.  While 
both  of  these  factors  undoubtedly  play  a  part,  their  inade- 
quacy in  explaining  the  stabiUty  of  all  emulsions  is  gener- 
ally admitted.  Not  only  does  the  stabiUty  of  emulsions 
not  universally  parallel  the  surface  tension  values  of  the 
liquids  making  up  a  given  dispersoid,  but  dilute  soap  solu- 
tions with  low  viscosity  act  as  better  emulsifying  agents 
than  more  viscid  glycerin  solutions.  More  recently  the 
importance  of  a  third  factor  has  been  emphasized  in  the 
maintenance  of  an  emulsion,  namely,  the  development  of 
an  encircling  film  about  the  droplets  of  the  divided  phase 
through  the  accumulation,  in  the  surface  between  oil  and 
dispersion  medium,  of  finely  divided  particles  of  a  third 
substance.  But  this  explanation,  too,  seems  adequate 
only  for  selected  examples  of  emulsions.  (See  pages  27 
to  29.) 

In  reviewing  the  empirical  instructions  available  for  the 
preparation  of  emulsions,  and  in  our  own  attempts  to 
formulate  such  as  would  always  yield  permanent  results,  we 
were  struck  with  the  fact  that  their  production  is  always 
associated  with  the  discovery  of  a  method  whereby  the 
water  (or  other  medium)  which  is  to  act  as  the  dispersing 
agent  is  all  used  in  the  formation  of  a  colloid  hydration 
(solvation)  compound.  In  other  words,  when  it  is  said  that 
the  addition  of  soap  favors  the  formation  and  stabilization 
of  a  division  of  oil  in  water,  it  really  means  that  soap  is  a 
hydrophilic  colloid  which,  with  water,  forms  a  colloid  hy- 
drate with  certain  physical  characteristics,  and  that  the  oil 
is  divided  in  this.  The  resulting  mixture  cannot,  there- 
fore, be  looked  upon  as  a  subdivision  of  oil  in  water,  but 
rather  as  one  of  oil  in  a  hydrated  colloid.     (See  page  29.) 

Evidence  is  adduced  showing  that  not  only  do  all  the 


6  FATS  AND  FATTY   DEGENERATION 

well  known  emulsification  methods  resort  to  the  use  of  hy- 
drophilic  colloids,  but  conversely,  through  the  use  of  any 
,hydrophilic  colloid  a  method  is  at  once  offered  by  which  a 
lasting  emulsion  may  be  produced.  Some  of  the  materials 
commonly  used  for  such  purposes,  and  a  discussion  of  such 
as  may  be  used,  are  taken  up  in  proof  of  this  contention. 

The  use  of  different  emulsifying  agents,  such  as  acacia, 
soap,  egg  yolk,  egg  white,  blood  albumin,  casein,  dextrin, 
gelatin,  agar,  etc.,  and  their  colloid-chemical  behavior  in 
the  formation  of  colloid  hydrates  are  analyzed  from  a  col- 
loid-chemical point  of  view.     (See  pages  30  to  31.) 

The  effects  of  the  colloid  itself,  of  its  concentration,  as 
well  as  the  effects  of  variations  in  the  concentration  of  the 
oil,  are  next  discussed.  The  oil  cannot  be  divided  into  a 
hydrated  colloid  until  a  certain  lower  limit  of  water  content 
has  been  exceeded,  nor  can  it  be  divided  permanently  into 
a  hydrated  colloid  after  an  upper  point  has  been  passed. 

The  enumerated  substances  do  not  all  act  equally  well. 
This  is  because,  in  the  production  of  a  hydrated  colloid, 
they  behave  differently  from  both  a  qualitative  and  quanti- 
tative view-point.  Best  results  are  obtained  with  those 
substances  which  not  only  have  the  power  of  taking  up 
much  water,  but  w^hich  yield  fairly  viscid  liquids  with  all 
amounts  of  water  that  may  be  added  to  them.  What  is 
wanted  is  a  relatively  homogeneous  liquid  of  sufficient 
tenacity,  by  which  is  meant  one  that  possesses  good  cover- 
ing power  together  with  great  cohesiveness.  (See  pages  31 
to  33.) 

The  action  of  casein  as  a  stabilizing  agent  is  particularly 
instructive.  Neutral  casein  does  not  absorb  much  water 
and  it  does  not  in  this  form  serve  for  the  preparation  of  an 
emulsion.  But  when  alkali  is  added,  it  develops  marked 
hydrophilic  properties,  upon  the  appearance  of  which  it 
becomes  one  of  the  best  stabilizing  agents  for  emulsions 
known.  It  might  be  thought  that  the  alkali  element  is  so 
important  because  it  forms  a  soap  in  contact  with  oil,  and 
soap  has  long  been  known  as  an  effective  emulsifier.     While 


THE  ARGUMENT  7 

some  such  action  no  doubt  occurs,  proof  that  tne  develop- 
ment of  hydrophilic  properties  by  the  casein  is  of  first  im- 
portance is  easily  presented  since  acid  (which  when  added 
to  neutral  casein  converts  it  into  a  hydrophilic  colloid) 
works  quite  as  effectively  as  does  alkali.  (See  pages  33 
to  35.) 

Emphasis  is  laid  upon  the  great  increase  in  viscosity 
which  emulsions  show  when  progressively  larger  amounts 
of  oil  are  added  to  a  given  amount  of  a  given  colloid  hydrate. 
Mixtures  are  prepared  in  this  way  which  show  maintenance 
of  form,  etc.,  in  other  words,  the  properties  of  solids,  even 
though  the  constituent  materials  from  which  they  were  pre- 
pared are  themselves  liquid  in  nature.    (See  pages  35  to  44.) 

III. 

Generally  speaking,  emulsions  are  broken  through  the 
institution  of  conditions  which  are  the  reverse  of  those  that 
make  for  their  stabilization;  in  other  words,  whenever  the 
hydrophilic  (lyophilic)  colloid  which  holds  the  aqueous  dis- 
persion medium  is  either  diluted  beyond  the  point  at  which 
it  can  take  up  all  the  offered  water,  or  is  so  influenced  by 
external  conditions  that  its  original  capacity  for  holding 
water  is  sufficiently  reduced.     (See  page  47.) 

Certain  emulsions,  as  those  of  oil  in  soap,  therefore, 
tend  to  break  on  simple  dilution.  But  agents  which  de- 
hydrate the  hydrophilic  colloid  act  even  more  rapidly  and 
effectively.  What  will  prove  to  be  an  effective  agent  in 
this  regard  depends,  of  course,  upon  the  character  of  the 
hydrophilic  colloid  stabilizing  the  emulsion.  When  alkali- 
casein  is  used,  the  addition  of  acid  breaks  the  emulsion; 
while  alkali  will  break  an  emulsion  stabilized  by  acid-casein. 
The  same  concentration  of  acid  or  alkali  is  without  effect 
upon  an  emulsion  stabilized  by  a  carbohydrate  hke  acacia 
or  dextrin.  Since  even  neutral  salts  will  dehydrate  an  acid- 
or  alkali-protein,  they  readily  serve  to  break  emulsions 
stabilized  by  these  substances.  An  emulsion  of  oil  stabi- 
lized in  soap  is  readily  broken  not  only  by  acids  and  various 


8  FATS  AND  FATTY  DEGENERATION 

salts,  but  also  by  alcohol.  Ether,  on  the  other  nand,  is 
relatively  ineffective.  Practically  all  these  substances  in 
low  concentration  are  without  effect  upon  emulsions  stabi- 
lized in  hydrated  carbohydrates. 

The  fact  that  alcohol  and  ether  are  by  themselves  thus 
relatively  ineffective  in  breaking  emulsions  explains  why 
the  ordinary  fat  extraction  methods  are  so  often  only  par- 
tially effective  in  getting  the  fat  out  of  biological  materials, 
and  why  previous  treatment  of  the  material,  as  by  diges- 
tion with  strong  acids  or  alkalies  and  by  similar  methods, 
yields  higher  fat  figures  than  extraction  with  ether  or  allied 
materials  alone.     (See  pages  47  to  53.) 

IV. 

The  experiments  on  emulsions  previously  detailed  are 
called  upon  in  the  interpretation  of  the  biological  behavior 
of  the  fat  in  the  cells  and  in  the  secretions  of  animals  and 
plants  under  physiological  and  pathological  conditions. 

The  problem  of  the  distribution  of  fat  in  Uving  cells  or 
in  various  secretions  from  the  living  tissues  may  be  sepa- 
rated into  two  divisions:  first,  a  chemical  one  deaUng  with 
such  questions  as  that  of  the  origin  and  transport  of  fat; 
and  second,  a  physical  one  asking,  for  example,  how  smaller 
or  larger  amounts  of  fat  may  be  stored  in  cells  without  at 
one  time  being  visible  or  demonstrable  by  micro-chemical 
methods,  while  at  another,  as  in  ''fatty  degeneration,"  they 
are  thus  demonstrable. 

There  is  scarcely  a  tissue  or  fluid  of  Irhe  body  which,  even 
in  the  poorest  states  of  nutrition,  does  not  contain  some  fat. 
But  even  the  smallest  amounts  of  fat  thus  found  exceed  the 
quantities  that  can  be  dispersed  in  permanent  form  in  pure 
water.  The  presence  of  such  amounts  of  fat  in  these  struc- 
tures, therefore,  at  once  presents  a  problem  identical  with 
that  which  asks  how  it  is  possible,  outside  of  the  body,  to 
maintain  a  fat  in  finely  divided  form  in  an  aqueous  disper- 
sion medium.  The  presence  of  any  amount  of  fat  in  a  cell 
or  tissue  exceeding  a  fraction  of  one  percent  is  possible 


THE  ARGUMENT  9 

only  because  the  tissues  contain  hydrophilic  colloids.  (See 
pages  57  to  62.) 

Looked  at  from  another  point  of  view,  even  the  smallest 
amounts  of  fat  ever  found  in  cells  sufl&ce  to  prove  that  the 
cell  contents  are  not  mere  aqueous  solutions  of  various 
salts  and  non-electrolytes  contained  in  a  semipermeable 
bag,  as  is  so  generally  believed  by  the  adherents  of  the 
osmotic  conception  of  cell  constitution. 

How  completely  the  notion  that  our  cells  are  filled  with 
salt  solutions  must  go  to  pieces,  becomes  clearly  evident 
when  it  is  recalled  that  certain  of  our  cells  and  tissues  con- 
tain even  normally  some  twenty  percent  of  fat  and  fat- 
like bodies.  Thus,  of  a  himdred  grams  of  nerve  tissue, 
seventy  grams  are  water  and  over  twenty  grams  are  fat. 
The  remainder  is  protein  chiefly.  Nerve  tissue  and  all 
tissues  which,  under  normal  or  abnormal  circumstances, 
hold  such  large  quantities  of  fat  are  able  to  do  so  only 
because  this  material  is  stabilized  in  a  finely  divided  state 
through  the  presence  of  hydrophilic  colloids  (like  proteins 
and  soap)  which  hold  the  water  of  the  cells  as  a  hydration 
compound.     (See  pages  62  to  64.) 

The  ^'soUd"  nature  of  many  tissues  with  preservation  of 
characteristic  ^ liquid"  properties  may  be  explained  through 
the  emulsion  character  of  the  tissues.  The  ^^ softening"  of 
tissues  observed  in  certain  pathological  studies  may  be 
understood  as  a  return  to  the  physical  properties  of  the 
individual  liquids  making  up  the  normal  emulsion  when 
this  is  ''broken." 

V. 

While  the  fat  in  the  cells  of  the  body  is  not  ordinarily 
visible  in  the  state  in  which  it  exists  here  normally,  certain 
pathological  conditions  popularly  termed  ''fatty  infiltra- 
tion" or  "fatty  degeneration"  sufiice  to  make  it  readily 
visible.  The  older  pathologists  believed  that  more  fat  was 
thus  visible  for  the  reason  that  the  cells  had  come  to  con- 
tain more,  either  because  it  had  been  brought  to  or  stored 


10         FATS  AND  FATTY  DEGENERATION 

in  the  cells,  or  because  their  protein  had  been  changed  to 
fat.  Modern  studies  of  the  question  have  proved  the  last 
of  these  possibilities  to  be  entirely  without  foundation,  so 
that  now  both  ^^ fatty  infiltration"  and  ^^ fatty  degenera- 
tion" are,  at  the  worst,  held  to  be  nothing  more  than 
states  in  which  an  excessive  deposition  may  occur.  But 
quantitative  chemical  studies  have  come  to  show  that  even 
the  worst  types  of  fatty  degeneration  in  tissues  may  yield 
no  fat  figures  lying  beyond  the  amounts  commonly  found  in 
these  same  localities  under  physiological  conditions.  In  the 
majority  of  instances,  chemical  analysis  fails  to  show  that 
the  affected  cells  contain  any  more  than  their  normal  fat 
content.  In  essence,  therefore,  ^^ fatty  degeneration"  no 
longer  represents  a  chemical,  but  a  physical  problem,  which 
asks  how  a  given  quantity  of  fat  usually  so  distributed  in  a 
cell  as  to  be  invisible,  becomes  re-distributed  in  such  fashion 
as  to  be  readily  visible.     (See  pages  67  to  69.) 

We  beheve  this  problem  is  identical  with  that  of  how  an 
emulsion  of  oil  in  protein  or  soap,  so  fine  that  the  individual 
oil  droplets  cannot  be  made  out  as  more  than  granules  even 
with  high  microscopic  magnification,  can  be  coarsened  to 
the  point  where  the  fat  granules  will  coalesce  to  form  more 
readily  visible  droplets.  As  a  matter  of  fact,  detailed  study 
of  the  conditions  which  are  necessary  for  the  production  of 
typical  ^^ fatty  degeneration"  in  tissues  shows  these  to  be 
identical  with  those  which  lead  to  the  partial  breaking  and 
coarsening  of  emulsions  of  the  type  of  oil-in-alkali  casein, 
oil-in-soap,  etc.     (See  pages  69  to  74.) 

The  various  substances  and  conditions  generally  listed  as 
capable  of  producing  a  '^ fatty  degeneration"  (phosphorus, 
lead,  arsenic,  mercury,  alcohol,  ether,  chloroform,  diabetes, 
local  circulatory  disturbances,  intoxication  with  acids,  etc.) 
are  all  of  them  means  by  which  the  normal  hydration 
capacity  of  the  soaps  or  of  certain  of  the  proteins  of  the  cell 
(as  the  globulins)  is  markedly  decreased.  The  matter  is 
best  illustrated,  perhaps,  by  detailing  a  specific  instance. 

When  a  cell,  in  consequence  of  injury,  is  made  the  subject 


THE   ARGUMENT  11 

of  an  acid  intoxication  by  any  of  the  direct  or  indirect  means 
enumerated  in  the  last  paragraph,  the  acid  makes  some  of 
the  proteins  of  the  affected  cells  swell,  while  another  group 
(the  globulins)  is  dehydrated  and  precipitated.  The  com- 
bination of  swelling  with  precipitation  yields  what  the 
pathologists  call  ''cloudy  swelling."  But  as  the  patholo- 
gists have  long  noted,  a  persistence  of  cloudy  swelling  is 
followed,  almost  as  a  rule,  by  a  ''fatty  degeneration"  of 
the  affected  cells.  On  the  basis  of  our  remarks,  this  coales- 
cence of  the  oil  droplets  into  the  larger  visible  ones  of  ''fatty 
degeneration"  is  dependent  upon  the  removal,  through  the 
action  of  the  acid,  of  some  of  the  stabilizing  effects  of  the 
proteins,  soaps  and  other  hydrophilic  colloids  contained  in 
the  cells.  The  increased  swelling  represents  a  dilution  of 
the  hydrophilic  colloids  of  the  cell,  while  the  clouding  rep- 
resents a  dehydration  of  certain  others.  (See  pages  74  to  76.) 
These  studies  on  emulsions  contribute  toward  the  expla- 
nation of  yet  another  pathological  observation.  When  any 
tissue,  as  a  portion  of  the  brain,  through  some  such  patho- 
logical disturbance  as  a  thrombosis,  is  deprived  of  its  nor- 
mal blood  supply,  the  affected  member  shows  first  a  cloudy 
swelling  accompanied  or  succeeded  by  a  "fatty  degenera- 
tion," and  then  a  "softening"  of  the  tissues.  How  at 
least  a  portion  of  this  (and,  we  are  inclined  to  think,  the 
major  portion  in  such  tissues  as  the  brain)  is  brought  about 
is  illustrated  in  the  changes  in  viscosity  observable  in  the 
preparation  of  an  emulsion  or  its  subsequent  destruction. 
Seven  percent  potassium  soap  and  cottonseed  oil,  for  in- 
stance, are  both  relatively  mobile  liquids,  but  when  mixed 
in  proper  proportion,  they  yield  an  emulsion  so  stiff  that  it 
will  stand  alone.  This  is  the  analogue  of  the  ten  to  twenty 
percent  emulsion  of  fat  and  lipoid  in  hydrated  protein  which 
we  call  nerve  or  brain.  If  the  oil-in-soap  emulsion  is  broken 
through  the  addition  of  a  little  acid  it  yields  an  impure 
mixture  of  oil,  water  and  precipitated  colloid  material  — 
the  analogue  of  the  liquid  contents  found  in  any  area  of 
brain  "softening."     (See  pages  76  to  85.) 


12         FATS  AND  FATTY  DEGENERATION 

VI. 

The  adipose  tissues  and  fatty  secretions  receive  separate 
consideration.  With  the  exception  of  these  two  biological 
materials,  protoplasm  represents  an  emulsion  of  fat-in- 
hydrated  colloid,  and  only  under  exceptional  circumstances 
does  the  proportion  of  fat  to  hydrated  colloid  exceed  twenty 
percent. 

When  the  fat  in  an  oil-in-hydrated  colloid  emulsion  is 
steadily  increased,  a  point  is  finally  reached  at  which  the 
emulsion  breaks  over  to  one  of  the  opposite  type,  namely, 
one  of  hydrated  colloid-in-oil.     (See  pages  89  to  91.) 

In  the  case  of  the  adipose  tissues  and  of  the  fatty  secre- 
tions, the  fat  figure  rises  to  fifty,  sixty,  and  even  eighty-five 
or  ninty  percent.  The  adipose  tissues,  too,  are  emulsions, 
but  the  increase  in  the  percentage  of  fat  has  been  carried 
beyond  the  critical  point  and  so  they  are  emulsions  of  the 
type  of  water-in-fat.  This  fact  accounts  for  the  constant 
finding  of  several  percent  of  water  in  the  adipose  tissues 
and  fatty  secretions.  The  reactions  to  paper,  to  feel,  and 
to  microscopic  examination  show  the  adipose  tissues  of  the 
body  and  many  of  the  fatty  secretions  to  be  emulsions  of 
hydrated  colloid-in-oil.  How  the  change  from  the  original 
type  of  oil-in-water  emulsion,  characteristic  of  ordinary  cell 
protoplasm,  to  the  type  of  water-in-oil,  characteristic  of 
adipose  tissues  and  the  fatty  secretions,  is  brought  about 
through  progressive  increase  in  the  concentration  of  the  fat 
is  illustrated  by  the  progressive  change  from  the  oil-in-water 
type  of  emulsion  which  we  call  milk  into  the  water-in-oil 
type  known  as  butter.  Separation  of  cream,  souring  of  the 
cream  and  churning  are  all  methods  which  ultimately  lead 
to  concentration  and  coalescence  of  the  fat  droplets  in  the 
original  milk  to  that  emulsion  of  hydrated  colloid-in-fat 
which  we  call  butter.     (See  pages  91  to  95.) 

The  conclusions  formulated  in  this  field  are  then  applied 
to  the  formation  of  ear  wax  and  of  other  fatty  secretions 
that  are  obtained  from  the  oil-in-hydrated  colloid  proto- 


THE  ARGUMENT  13 

plasm  which  makes  up  the  secreting  cells  from  which  these 
secretions  are  obtained.     (See  pages  95  to  96.) 

The  striking  optical  changes  which  accompany  the  grad- 
ual dehydration  of  the  oil-in-hydrated  colloid  emulsion  are 
commented  upon  and  their  importance  in  the  interpreta- 
tion of  various  biologic  phenomena  touched  upon.  (See 
pages  96  to  101.) 

vn. 

In  passing  from  the  ordinary  tissue  cell  which  represents 
a  fine  emulsion  of  fat  in  a  hydrated  protein,  to  the  cell 
which  is  characteristic  of  the  adipose  tissues,  essentially  an 
emulsion  of  hydrated  protein-in-fat,  we  observe  the  conse- 
quences incident  to  a  progressive  increase  in  the  concen- 
tration of  the  fat  in  an  oil-in-water  type  of  emulsion  to 
beyond  the  critical  point.  If  we  look  at  the  results  of  the 
opposite  type  of  change,  namely  that  of  increasing  the 
amount  of  water  in  the  ordinary  fat-in-hydrated  colloid 
which  constitutes  our  cells,  we  find  that  this  leads  to  the 
production  of  milk.     (See  page  105.) 

Normal  milk  production  represents  just  such  a  set  of 
changes.  The  originally  cubical  cells  which  make  up  the 
alveoli  of  an  active  mammary  gland  become  richer  in  water 
and  filled  with  granules  (cloudy  sweUing)  while  the  fat  in 
the  cells  nms  together  into  more  readily  A^sible  droplets 
(fatty  degeneration).  When  this  process  of  cloudy  swell- 
ing with  fat  coalescence  becomes  sufficiently  great,  the  cell 
bursts  and  a  fluid  mixture  of  hydrated  colloids  containing 
fat  globules  results.     This  is  milk.     (See  pages  105  to  107.) 

By  making  use  of  the  laws  governing  the  making  and 
maintenance  of  emulsions,  it  is  readily  possible  to  make 
cow's  milk  or  any  other  kind  artificially,  whenever  the 
necessary  chemical  constituents  are  available.  To  do  this 
it  is  only  necessary  to  take  the  proteins  characteristic  of 
the  milk  desired,  hydrate  these  to  the  point  at  which  the 
natural  fat  of  the  milk  (or  some  other  fat)  may  be  readily 
emulsified  in  them,  and  then  dilute  the  mixture  to  the 


14  FATS  AND  FATTY   DEGENERATION 

necessary  amount.  To  it  may  then  be  added  the  various 
salts,  sugars,  or  other  materials  that  are  needed  to  give  the 
milk  its  requisite  composition.     (See  pages  108  to  111.) 

VIII. 

The  ordinary  view,  that  a  secretion  is  not  given  off  ''as 
such"  but  that  there  is  first  a  secretion  of  water  which 
then  leaches  out  from  the  secreting  membrane  the  dissolved 
substances  characteristic  of  the  secretion,  meets  with  diffi- 
culties when  the  secretion  contains  not  only  crystalloids 
(which  readily  diffuse  through  the  colloids  which  constitute 
our  secreting  membranes)  but  the  non-diffusing  colloids. 
In  an  attempt  to  explain  the  production  of  the  mucoid 
secretions,  for  example,  it  seems  most  probable  that  these 
are  thrown  off  in  practically  non-hydrated  form  and  then 
swell  upon  the  surfaces  of  the  secreting  membranes  when 
water  is  added  to  them.  A  model  is  described  which  illus- 
trates this  idea  physico-chemically.  Some  acacia  granules 
are  ground  in  cottonseed  oil.  When  a  drop  of  this  material 
is  put  under  the  microscope  and  a  little  water  is  permitted 
to  come  in  contact  with  one  edge  of  it,  active  surface  move- 
ments begin  and  the  particles  of  the  acacia  are  thrown 
upon  the  surface  of  the  oil  droplet.  Here  they  imbibe 
water  and  swell  to  form  a  mucoid  mass  covering  the  surface 
of  the  oil  droplet. 

The  set  of  changes  in  this  model  and  those  observable 
in  living  cells  are  so  strikingly  alike  that  the  suggestion 
seems  justified  that  the  forces  active  in  the  two  are  also 
much  the  same.     (See  pages  115  to  118.) 

IX. 

The  problem  of  growth  is  divided  by  the  experimental 
morphologists  into  two  divisions:  growth  proper  and  dif- 
ferentiation. 

The  former  is  best  defined  as  an  increase  in  volume,  the 
energy  for  which  colloid-chemical  study  has  found  in  the 


THE  ARGUMENT  15 

swelling  of  the  colloids  of  the  involved  cells,  tissues  or  organs. 
When  for  internal  or  external  reasons  there  occur  inequali- 
ties in  such  swelling,  stresses  are  produced  which  bring 
with  them  the  first  elements  of  differentiation  in  the  grow- 
ing protoplasm.  Such  differentiation  is  subsequently  further 
and  more  obviously  aided  and  abetted  by  changes  in  the 
physical  state  of  the  growing  colloid  masses  as,  for  example, 
the  precipitation  of  certain  of  the  colloids.  (See  pages  121 
to  123.) 

A  series  of  figures  is  shown  illustrating  the  wealth  of 
structure  produced  whenever  simple  hydratable  colloids, 
mixtures  of  such,  or  emulsions  containing  different  chemical 
constituents,  are  subjected  to  the  stresses  incident  to  dry- 
ing, to  the  addition  of  water,  or  to  the  physical  and  chemical 
effects  incident  to  the  addition  of  various  extraneous  sub- 
stances, etc. 

Structures  which  are  finely  granular,  coarsely  granular 
and  alveolar  are  described.  Structures  simulating  growing 
connective  tissue,  involuntary  muscle,  or  sarcoma  are  shown. 
How  the  fine  markings  of  the  skin,  and  how  such  appar- 
ently complex  structures  as  carcinomatous  pearls  or  whorls 
may  be  imitated  is  also  touched  upon.  (See  pages  123  to 
138.) 

A  final  paragraph  shows  how  the  protective  coverings  of 
plants,  like  those  which  make  waterproof  the  leaves  and 
fruits,  may  be  formed  through  the  drying  of  oil-in-water 
types  of  emulsions  into  the  water-in-oil  types.  (See  pages 
138  to  140.) 

X. 

The  final  chapter  attempts  to  point  out  the  significance 
of  the  study  of  the  emulsions  for  the  problems  of  applied 
chemistry,  of  biology  and  of  medicine. 

By  substituting  definite  laws  for  the  empirical  in  the 
production,  maintenance  and  destruction  of  emulsions,  they 
are  of  importance  to  the  pharmaceutical  chemist,  the  pur- 
veyor of  food,  the  dairyman  and  the  manufacturer.     By 


16         FATS  AND  FATTY  DEGENERATION 

touching  upon  the  normal  fat  content  of  cells,  the  nature 
of  ^'cell  membranes,"  the  state  of  the  fat  in  the  adipose 
tissues,  the  mechanism  of  the  formation  of  the  fatty  secre- 
tions and  that  of  the  oily  protective  coverings  character- 
istic of  plants  and  animals,  these  studies  are  of  importance 
to  the  biologist.  By  aiding  in  the  explanation  of  the  nature 
of  fatty  degeneration,  and  by  thus  contributing  to  a  further 
analysis  of  what  is  reversible  and  what  irreversible  in  the 
series  of  changes  which  characterize  the  reaction  of  proto- 
plasm to  injury,  these  emulsion  studies  are  of  interest  to 
the  thinker  in  modern  medicine.     (See  pages  143  to  146.) 


II.  ON  THE  MAKING  OF  EMULSIONS. 


II.  ON  THE  MAKING  OF  EMULSIONS. 
1.   INTRODUCTION. 

The  following  pages  are  the  outgrowth  of  the  attempt, 
begun  some  years  ago,  to  get  an  answer  to  the  problem  of 
the  nature  and  causes  of  ^^ fatty  degeneration"  and  of  cer- 
tain biological  phenomena  which  are  closely  associated 
therewith,  like  the  formation  of  milk,  the  production  of 
the  oily  secretions,  and  the  origin  of  the  protective  cover- 
ings of  plants.  There  appeared  to  us  a  rough  analogy  be- 
tween the  available  facts  covering  these  physiological  and 
pathological  processes  and  the  behavior  of  emulsions.  In 
following  this  lead  more  closely  we  observed,  however,  that 
there  still  existed  great  gaps  in  what  had  been  written  re- 
garding the  physics  of  the  emulsions  themselves.  Since  a 
knowledge  at  least  of  the  main  facts,  if  not  of  the  whole 
theory,  of  the  behavior  of  emulsions  was  requisite  to  our 
biological  purposes,  we  found  it  necessary  to  go  back  to  a 
study  of  the  emulsions  themselves. 

The  general  problem  of  the  deposition  of  fat  in  living 
cells  and  body  fluids,  under  both  physiological  and  patho- 
logical conditions,  divides  quite  naturally  into  two  parts: 
a  first,  concerned  with  the  chemical  question  of  the  origin 
and  transport  of  fat ;  and  a  second,  dealing  with  the  physical 
question  of  how  large  amounts  of  the  substance  may,  at 
one  time,  be  stored  in  a  cell  without  being  visible  or  de- 
monstrable by  micro-chemical  methods,  while  the  same 
amount,  at  another  time,  as  in  ''fatty  degeneration,"  is 
readily  visible  and  easily  demonstrable.  This  volume  bears 
little  upon  the  first  of  these  problems;  its  main  piupose  is 
to  indicate  the  illuminating  help  which  the  concepts  of 
colloid  chemistry  may  give  the  second. 

Since  all  these  biological  problems  are  to  our  mind  inti- 

19 


20 


FATS  AND  FATTY  DEGENERATION 


mately  associated  with  those  of  the  making,  maintenance 
and  breaking  of  emulsions,  a  study  of  the  general  physical 
chemistry  of  these  systems  is  first  in  order. 

The  emulsions  are  of  much  interest  from  both  practical  and 
theoretical  points  of  view.  Not  only  do  large  quantities  of 
economically  important  materials  come  to  us  in  the  form  of 
emulsions  (as  milk,  egg  yolk,  rubber,  etc.),  but  the  making 
and  breaking  of  these  is  a  matter  of  great  economic  and 
scientific  concern.  The  problem  of  how  an  emulsion  may 
be  produced  appears  in  the  biological  phenomena  con- 
cerned with  the  formation  of  mammalian  milk,  the  ^'milk" 
of  plants,  etc.;  while  that  of  the  breaking  of  emulsions 
comes  to  us  in  the  problems  of  butter  manufacture,  of  the 
manufacture  of  emulsions  used  in  therapeutics,  in  certain 
aspects  of  ''fatty  degeneration,"  etc. 


2.   DEFINITION  AND  TYPES   OF  EMULSIONS. 

In  its  simplest  form,  an  emulsion,  as  a  mixture  of  two 
immiscible  liquids,  is  a  diphasic  system.     Since  one  liquid 

is  subdivided  in  the  other, 
an  emulsion  constitutes  a 
dispersed  system,  according 
to  the  terminology  of  Wolf- 
gang OsTWALD.^  Once  the 
materials  to  make  up  an 
emulsion  and  their  quanti- 
ties are  settled  upon,  it 
would  seem,  at  first  sight, 
of  no  consequence  how 
these  materials  are  divided 
into  each  other  to  yield  the 
dispersed  system.  Definite 
Fig,  1,  quantities  of  water  and  oil, 

for  example,rwould  seem 
destined  always  to  yield  the  same  end  product.     But  as 

1  Wolfgang  Ostwald:  Handbook  of  Colloid  Chemistry,  24,  Trans,  by 
Fischer,  Oesper  and  Berman,  Phila.,  1915. 


ON  THE  MAKING  OF  EMULSIONS  21 

indicated  in  the  important  studies  of  Walther  Ostwald  ^ 
and  T.  B.  Robertson,^  these  materials  are  capable  of 
forming  two  entirely  different  kinds  of  emulsions:  a  firsts 
consisting  of  oil  in  water,  and  a  second,  of  water  in  oil.  In 
the  former,  the  oil  is  the  divided  phase  and  the  water  the 
continuous  one;  in  the  second,  the  water  is  the  divided 
phase  and  the  oil  the  continuous  one.  The  matter  is  illus- 
trated diagrammatically  under  A  and  B  in  Figure  1.  The 
two  emulsions  have  totally  different  properties,  as  evidenced, 
for  instance,  by  their  different  viscosities,  by  their  different 
^^feel"  and  by  their  different  abilities  to  "wet*'  or  "oil" 
paper  dipped  into  them. 

3.   EXPERIMENTS   ON   EMULSIONS. 

We  shall  take  up  now  a  more  detailed  study  of  a  few 
emulsions  in  order  to  famiharize  oiu^elves  with  their  gen- 
eral properties.  We  chose  for  the  purpose  emulsions  which, 
from  a  chemical  point  of  view,  consist  of  mixtures  of  oil  and 
water.  From  a  physical  point  of  view  they  are,  unless 
otherwise  noted,  of  the  "  oil-in- water "  type  mentioned 
above,  the  oil  being  the  divided  phase,  the  aqueous  dis- 
persion medium  the  continuous,  enveloping  one.  The  oil 
referred  to  in  these  experiments  is  highly  purified  cotton- 
seed oil.  Throughout  the  volume  we  speak  of  water  as  the 
second  phase  in  our  emulsions.  As  will  be  seen  shortly, 
this  is  done  for  brevity,  for,  strictly  speaking,  it  is  not  cor- 
rect. These  experiments  will  show  that  the  aqueous  phase 
is  most  commonly  a  hydration  compound  formed  from 
combination  of  a  protein,  a  soap,  acacia  gum,  or  some 
other  hydrophiUc  colloid,  with  water,  so  that  the  emulsion 
under  discussion  becomes  most  frequently  not  a  dispersion 
of  oil  in  water,  but  one  of  oil  in  a  hydrated  soap,  in  a  hy- 
drated  albumin,  or  something  of  the  sort. 

We  know  of  no  instance  in  which  oil  in  contact  with  pure 
water  or  a  watery  dispersion  medium  leads  spontaneoiLsly 

^  Walther  Ostwald:  KoUoid-Zeitschrift,  6,  103  (1910);  7,  64  (1910). 
2  T.  B.  Robertson:  KoUoid-Zeitschrift,  7,  7  (1910). 


22 


FATS  AND  FATTY   DEGENERATION 


to  the  formation  of  an  emulsion.  In  certain  manufacturing 
processes,  and  under  biological  circumstances,  conditions 
are  sometimes  instituted,  or  come  to  pass,  which  allow  an 
oil  to  appear,  or  to  be  produced,  in  very  fine  particles  which 
are  then  kept  discrete.  When  milk  is  formed  in  nature,  or 
when  fat  is  deposited  in  cells  through  the  combination  of 
fatty  acid  with  glycerin,  the  fat  appears  from  the  beginning 
in  a  state  of  fine  subdivision  and  may  be  maintained  thus. 
But  under  laboratory  conditions,  this  fine  division  of  a  fat 
in  a  watery  phase  can  be  obtained  only  by  mechanical 
methods. 

We  used  such  methods  in  our  experiments.  When  small 
quantities  of  an  emulsion  are  to  be  made,  mortars  do  very 

well,  as  the  pharmacists  have 
long  known.  Larger  quanti- 
ties are  better  prepared  in 
mechanical  mixers  of  the 
type  shown  in  Figure  2. 
The  contents  of  the  octag- 
onal glass  jar  a  are  effec- 
tively beaten  by  the  stiff 
stirrer  h  which  may  be 
turned  at  any  speed  desired 
by  the  pulley  arrangement  c 
connected  by  means  of  the 
belt  d  with  a  motor.  When 
comparative  experiments 
need  to  be  done  and  con- 
ditions for  mixing  have  to  be  kept  constant,  a  series  of 
mixers  as  constructed  for  us  by  our  mechanician  Josef 
KuPKA  and  shown  in  Figure  3  is  run  at  the  same  speed 
by  means  of  a  continuous  belt. 

As  will  become  better  apparent  later,  the  process  of  mak- 
ing  an  emulsion  is  something  totally  different  from  that  of 
maintaining  it  after  it  is  made.  To  make  an  emulsion 
showing  a  high  degree  of  subdivision  is  not  always  easy. 
The  accomplishment  of  the  necessary  mechanical  subdi- 


FiG.  2. 


ON  THE  MAKING  OF  EMULSIONS 


23 


vision  offers,  at  times,  great  difficulties.  When  light  oils 
only  are  to  be  considered  —  as  cottonseed  oil  or  the  Ughter 
hydrocarbon  oils  —  and  an  extreme  grade  of  subdivision  is 
not  desired,  the  emulsifier  of  the  type  shown  in  Figure  2 
will  suffice.     But  if  very  fine  emulsions  are  sought,  the  stir- 


FiG.  3. 


ring  or  rotary'  action   of  this  device  must   be  combined 
with  pressure. 

The  reasons  for  this  are  about  as  follows:  to  divide  a 
liquid,  it  must  be  torn.  Any  rotary  motion  will  accomplish 
this  to  a  certain  extent.  But  if  the  rather  large  droplets 
thus  produced  are  to  be  made  smaller,  the  force  producing 
the  tearing  must  be  increased.  Speeding  the  rotary  motion 
helps  in  this  regard,  but  only  to  a  certain  point.  It  was 
Emil  Hatschek,^  so  far  as  we  know,  who  first  showed  that 
the  force  required  to  divide  a  drop  of  any  Hquid  mounts 
tremendously  as  the  size  of  the  droplet  decreases.  A  rotary 
1  Emil  Hatschek:  KoUoid-Zeitschrift,  6,  254  (1910);  7,  81  (1010). 


24 


FATS  AND  FATTY  DEGENERATION 


motion  acting  upon  liquid  droplets  floating  in  a  second 
liquid  does  not  therefore  accomplish  subdivision  beyond  a 
certain  point.  This  point  is  determined  by  the  kind  and 
speed  of  the  emulsifying  flail,  but  much  more  by  the  vis- 
cosity of  the  oil  to  be  divided  and  the  viscosity  of  the 
medium  into  which  it  is  being  divided.  When  the  dis- 
persing medium  is  of  a  type  to  which,  in  a  sense,  the  oil 
will  '^  stick,  ^'  allowing  this  therefore  to  be  torn  across  the 
face  of  the  dispersing  medium,  the  best  possible  division  of 
the  oil  is  accomplished.  The  oil  droplets  are  caught  be- 
tween the  edge  of  the  flail  and  a  wall  of  stiff  dispersing 
medium.  Rotary  motion  therefore  becomes  reinforced  by  a 
cutting  action  and  pressure.  Rotary  motion  combined  with 
pressure  leads  to  the  greatest  possible  division. 

These  considerations  will  show  why,  first  of  all,  the  old 
method  of  preparing  emulsions  in  a  mortar  gave  such  good 
results.  The  rotary  motion  of  the  pestle  is  such  as  to  tear 
any  liquid  (oil)  over  the  face  of  the  dispersing  medium  while 

the  pressure  on  the  pestle 
aids  in  dividing  the  drop- 
lets more  and  more  finely. 
To  get  extreme  division, 
a  homogenizer  is  therefore 
of  great  service.     Various 
designs  of  these  have  long 
been  used  in  the  dairy  in- 
dustry.    Diagrammatic 
representation   of  the  es- 
sential part  of  a  pattern 
which  in  our  hands  yielded 
good  results  is  shown  in 
Figure  4.     After  a  rel- 
atively coarse  emulsion 
has  been  prepared  by  any 
convenient  method,  it  is  poured  into  the  metal  funnel  A 
within  which  turns  the  pestle  C  upon  which  any  amount 
of  pressure  may  be  exerted  through  a  screw  at  the  top. 


Fig.  4. 


ON  THE  MAKING  OF  EMULSIONS  25 

To  escape,  the  emulsion  passes  under  hydraulic  pressure 
between  the  grinding  and  pressure 
surfaces  of  C  and  B.  Since  these 
surfaces  are  bevelled,  as  shown  in 
the  diagram,  the  larger  oil  droplets 
entering  above  are  gradually  re- 
duced in  size  before  they  are  per- 
mitted to  escape  at  D  below. 

4.   ON   THE   MAKING   OF 
EMULSIONS. 

§1. 
WTiile  the  mere  contact  of  cotton- 
seed oil  with  water  will  not  spon- 
taneously lead  to  the  formation  of 
an  emulsion,  it  is  possible  to  pro- 
duce this  result  by  simply  beating 
the  two  together.  But  the  amount 
of  oil  that  may  be  emulsified  in  pure 
water  is  very  small.  It  suffices 
merely  to  impart  a  milky  tinge  to 
the  water,  and  quantitative  experi- 
ments indicate  that  less  than  one- 
half  of  one  percent  of  cottonseed 
oil  may  thus  be  distributed  into 
water  with  a  fair  degree  of  per- 
manence. In  Figure  5  is  shown 
the  effect  of  active  agitation  for  24 
hours  of  2  cc.  of  cottonseed  oil  in 
98  cc.  of  distilled  water.  Within  a 
few  hours  after  the  mixture  is 
poured  into  a  cylinder,  almost  the 
entire   oil  has   separated   out   as   a 


clear  layer  above  the  slightly  milky  jtjq  5 

water.     No    one   has  reported    the 

permanent  emulsification  of  oil  in  pure  water  in  amounts 
exceeding  two  percent.     This  is  the  value  obtained   by 


26  FATS  AND  FATTY  DEGENERATION 

Wm.  C.  McC.  Lewis  ^  with  mineral  oil.  The  oil  particles 
in  these  emulsions  are  rather  small,  their  dimensions  lying 
within  the  realm  of  the  colloid  degrees  of  division.  These 
low  concentrations  of  oil  in  water,  therefore,  really  repre- 
sent colloid  suspensions  of  oil  in  water  and  possess  not  only 
the  characteristic  stability  of  such  systems,  but  also  their 
well-known  saturation  limit. ^ 

As  we  ordinarily  use  the  term  '^ emulsion,"  we  mean  the 
subdivision  of  one  fluid  in  a  second  in  amounts  exceeding 
these  low  values.  The  mixture  must,  moreover,  show  a  fair 
degree  of  stability;  in  other  words,  the  two  liquids  consti- 
tuting the  dispersoid  must  not  separate  in  the  course  of 
weeks,  months  or  years.  A  temporary  subdivision  of  large 
quantities  of  oil  in  a  given  volume  of  water,  or  the  converse, 
can,  of  course,  be  obtained  by  merely  beating  the  two  to- 
gether. The  'problem  of  emulsification,  therefore,  really  resolves 
into  two  parts:  first,  the  question  of  how  an  emulsion  may  be 
produced;  second,  how  when  once  the  subdivision  of  the  oil  in 
the  water  has  been  accomplished,  this  subdivision  can  be,  or  is, 
stabilized.  These  two  problems  have  not  always  been  held 
apart  as  they  should  be.  Failure  to  distinguish  between 
them  has  given  rise  to  purposeless  and  often  bitter  debate. 
In  a  certain  sense  the  first  of  these  two  problems  is  essen- 
tially a  mechanical  one,  upon  the  nature  of  which  we  have 
already  touched,  but  since  this  mechanical  problem  is  often 
intimately  dependent  upon,  or  connected  with  the  physical 
properties  of  the  medium  into  which  the  subdivision  is 
being  made,  while  these  physical  properties,  in  their  turn, 
are  connected  with  the  question  of  the  nature  and  the  action 
of  the  various  ^^emulsifying  agents"  used,  it  becomes  read- 
ily intelligible  why  the  two  problems  have  been  so  con- 
stantly confounded.  Having  discussed  the  mechanical 
portions  of  the  problem,  we  therefore  turn  to  those   con- 

1  Wm.  C.  McC.  Lewis:  Kolloid-Zeitschrift,  4,  211  (1909). 

2  For  references  to  the  literature  dealing  with  this  problem  see  Wolfgang 
Ostwald:  Handbook  of  Colloid-Chemistry,  136,  Trans,  by  Fischer,  Oesper 
and  Berman,  Phila.,  1915. 


ON  THE  MAKING  OF  EMULSIONS  27 

cemed  with  the  stabihzation  of  the  subdivision  —  in  reahty, 
that  part  of  the  general  theory  of  emulsification  upon  which 
most  effort  has  been  expended  by  those  who  have  busied 
themselves  with  this  general  subject. 

Different  workers  have  suggested  different  factors  as  the 
causes  of  the  stabihzation.  Generally  speaking,  they  have 
all  striven  to  discover  some  one  or  two  elements  as  exclu- 
sively responsible  for  it.  We  question  whether  this  can  be 
done  successfully.  While  we  wish  to  leave  detailed  dis- 
cussion of  the  theoretical  aspects  of  the  problem  to  a  later 
time  when  longer  and  more  careful  series  of  measurements 
have  been  made  than  are  as  yet  available  on  the  properties 
of  various  liquids  which  may  be  used  successfully  in  the 
production  of  stabile  emulsions,  even  such  experiments  as 
are  now  described  by  different  authors,  or  have  been  made 
by  ourselves,  already  indicate  that  a  group  of  different 
factors  plays  a  role,  the  relative  importance  of  each  of 
which  varies  not  only  in  different  emulsions,  but  in  one 
and  the  same  emulsion  under  different  circumstances. 

The  most  generally  accepted  factors  that  are  held  to  be 
of  great  and  general  importance  in  the  maintenance  of  an 
emulsion  are  those  suggested  by  S.  Plateau  ^  and  G. 
Quincke.^  While  these  authors  directed  chief  study  to 
foams,  the  structm-e  of  these  (as  dispersions  of  a  gas  in  a 
hquid)  has  usually  been  regarded  as  so  closely  related  to 
that  of  emulsions  (dispersions  of  one  hquid  in  a  second) 
that  the  conclusions  reached  from  investigation  of  the  one 
set  of  systems  have  been  held  apphcable  wdth  httle  modi- 
fication to  the  second. 

Plateau  and  Quincke  held  the  permanence  of  foams 
and  emulsions  to  depend  chiefly  upon  the  shght  surface 
tension  of  the  dispersing  medimn  and  its  high  viscosity. 
While  both  these  factors  undoubtedly  play  a  part,  some 
obvious  shortcomings  in  the  theory  have  been  emphasized 

1  S.  Plateau:  Ann.  der  Physik.,  141,  44  (1870). 

2  G.  Quincke:  Ann.  der.  Physik.,  271,  580  (1888). 


28  FATS  AND   FATTY   DEGENERATION 

by  H.  W.  HiLLYER  ^  and  S.  U.  Pickering.^  Thus  liquids, 
which  from  consideration  of  their  surface  tension  would 
seem  to  be  ideal  for  the  production  of  permanent  emulsions, 
fail  in  practice;  and  dilute  soap  solutions  of  relatively  low 
viscosity,  for  example,  turn  out  to  be  better  emulsifying 
agents  than  more  viscid  glycerins.  In  this  connection, 
HiLLYER  has  made  a  fundamental  contribution  to  the  whole 
question  by  emphasizing  that  to  obtain  a  proper  measure 
of  the  sm^ace  tension  relationships  active  in  an  emulsion, 
the  surface  tension  of  the  dispersing  phase  must  not  be 
measured  against  air  (which  would  be  proper  only  in  the 
case  of  air-foams)  but  against  the  second  material  entering 
into  the  composition  of  the  emulsion  (the  oil). 

Pickering  has  brought  out  the  importance  of  a  third 
factor  in  the  maintenance  of  an  emulsion,  namely,  the  ac- 
cumulation of  finely  divided  particles  of  a  third  substance 
in  the  surface  between  oil  and  dispersion  medium.  He 
assumes  that  these  particles  surround  the  oil  droplets  like  a 
film.  This,  too,  undoubtedly  plays  a  part  in  the  stabiliza- 
tion of  a  selected  number  of  emulsions.  Our  personal  ob- 
jection to  Pickering's  conclusions  is  only  a  quantitative 
one.  In  explaining  the  stability  of  such  an  emulsion  as 
that  of  oil  in  soap,  for  instance,  he  needs  to  assume  the 
soap  always  to  be  contaminated  with  stearin  particles,  a 
view  that  is  hardly  justified,  for  it  is  possible  to  obtain  and 
work  successfully  with  soap  entirely  free  from  such. 
Wilder  D.  Bancroft^  is  in  sjnnpathy  with  Pickering's 
conclusions  in  that  he  also  emphasizes  the  importance  for 
stabilization  of  the  formation  of  a  third  phase  between  the 
two  materials  emulsified  in  each  other.  This  view  of  the 
importance  of  the  production  of  an  interfacial  film  which 
then  keeps  the  dispersed  particles  from  coalescing,  is  also 
accepted  by  G.  H.  A.  Clowes.^     Depending  then  upon 

1  H.  W.  Hillyer:  Jour.  Amer.  Chem.  Soc,  25,  511  (1903);  ibid.,  25,  524 
(1903). 

2  S.  U.  Pickering:  KoUoid-Zeitschrift,  7,  15  (1910). 

3  Wilder  D.  Bancroft:  Jour.  Physical  Chem.,  17,  501  (1913). 
*  G.  H.  A.  Clowes:  Jour.  Physical  Chem.,  20,  415  (1916). 


ON  THE  MAKING  OF  EMULSIONS  29 

changes  in  surface  tension  as  induced  through  the  addition 
of  various  chemicals,  for  example,  Clowes  holds  this  film 
to  be  bent  in  the  one  or  the  other  direction,  thereby  yielding 
in  the  one  instance  an  oil-m- water  type  of  emulsion,  in  the 
other  one  of  water-in-oil. 

§2. 

In  reviewing  the  empirical  instructions  available  for  their 
preparation,  and  in  our  own  attempts  to  formulate  such  as 
would  always  yield  permanent  emulsions,  we  were  struck 
with  the  fact  that  success  in  this  direction  is  best  attain- 
able through  the  discovery  of  a  method  whereby  the  water 
(or  other  medium),  which  is  to  act  as  the  dispersing  agent, 
is  all  used  in  the  formation  of  a  colloid  hydration  (solva- 
tion) compound.  In  other  words,  an  oil-in-water  emulsion 
is  markedly  stabiUzed  only  through  the  addition  of  colloid 
to  the  watery  phase.  Empirically,  this  fact,  too,  has  long 
been  recognized  although  we  question  whether  it  has  been 
fully  understood  what  kind  of  colloid  will  produce  stabili- 
zation and  why  this  is  effected.  An  emulsion  is  stabilized 
only  through  the  addition  of  a  lyophilic  (hydrophilic)  colloid. 
The  amount  of  colloid  necessary  is  relatively  great.  It  must  be 
sufficient,  at  least  in  the  production  of  an  emulsion,  to  bind  all 
the  water  if  an  emulsion  showing  real  permanence  is  to  be 
produced.  Differently  expressed,  the  production  of  a  lasting 
emulsion,  as  of  oil  in  water,  is  really  never  obtainable  through 
the  division  of  the  former  into  the  latter,  but  only  through  the 
division  of  the  oil  into  a  hydrated  (solvated)  colloid} 

1  Both  W.  D.  Bancroft  and  G.  H.  A.  Clowes  at  the  Urbana  (1916) 
meeting  of  the  American  Chemical  Society,  in  their  discussion  of  our  own 
views  regarding  the  importance  of  colloid  solvates  (colloid  hydrates)  for  the 
stabilization  of  emulsions,  found  in  our  views  something  irreconcilable  mth 
their  notions  of  the  importance  of  interfacial  films  and  of  surface  tension 
changes  in  these.  While  we  do  not  wish  to  insist  upon  a  harmony  where 
such  may  not  be  desired,  there  is,  of  course,  nothing  mutually  exclusive  in 
the  ideas  of  solvation,  of  changes  in  surface  tension,  and  —  at  times  —  the 
formation  of  a  continuous  third  phase  between  the  two  chief  substances  mak- 
ing up  an  emulsion.  When  "water,"  according  to  our  notion,  becomes  a 
"colloid  hydrate,"  the  properties  of  the  second  liquid  are  different  from  those 


30         FATS  AND  FATTY  DEGENERATION 

§3. 

The  truth  of  these  assertions  is  best  illustrated  by  in- 
vestigating, from  this  colloid-chemical  point  of  view,  any 
of  the  empirically  well-established  methods  generally  used 
in  the  production  of  emulsions.  A  good  illustration  and 
one  applicable  to  most  oils  is  the  following: 

One  part  by  weight  of  powdered  acacia  is  ground  in  a 
mortar  with  two  parts  by  weight  of  oil.  To  this  is  added 
slowly  and  with  constant  grinding,  one  part  by  weight  of 
water.  As  the  trituration  is  continued,  a  second  part  of 
water  is  stirred  in  and  finally  a  third.  This  emulsion  will 
then,  in  most  instances,  stand  heavy  further  dilution  with 
water  without  the  oil  separating  out  in  coarse  form. 

This  method  yields  an  excellent  emulsion.  In  reviewing 
the  factors  that  contribute  to  this  end,  let  it  first  be  noted 
that  the  acacia  used  is  a  strongly  hydrophilic  colloid.  Sec- 
ond, the  amount  employed  is  relatively  high.  In  the  terms 
of  what  was  said  above,  at  least  enough  colloid  was  used  to 
bind  all  the  water.  The  resultant  emulsion  is,  therefore,  in 
no  sense  to  be  regarded  as  one  of  oil  in  water  but  rather  as 
one  of  oil  in  a  hydrated  colloid. 

of  the  first,  and  these  properties  include  surface  tension,  viscosity  and  dis- 
tribution between  two  phases.  But,  we  repeat,  these  factors  to  which  Pla- 
teau, Quincke  and  Pickering  first  directed  attention  are  not  by  themselves 
able  to  explain  all  the  phenomena  observed.  Where  Clowes  holds  that  an 
emulsion  of  oil  is  stabihzed  through  sodium  oleate  because  the  substance 
reduces  the  surface  tension  of  water,  we  would  say  that  stabilization  has 
ensued  because  the  oil  has  been  divided  into  a  highly  hydratable  sodium  soap. 
When  the  addition  of  calcium  destroys  this  emulsion,  it  is  not  because  of  com- 
pUcated  changes  in  a  surface  film,  but  simply  because  calcium  oleate  is  an  only 
slightly  hydratable  soap.  Free  water,  in  consequence,  appears  in  the  mixture, 
and  the  oil  separates  out  in  gross  form,  as  described  above,  for  only  very  little 
oil  can  be  permanently  subdivided  in  "  pure  "  or  "  free  "  water.  We  describe 
the  consequences  of  such  changes  from  highly  hydratable  to  less  hydratable 
soaps  upon  the  stability  of  an  emulsion  on  page  49. 

Neither  do  we  wish  our  statement  that  an  agreement  is  possible  between 
Clowes'  and  our  views  on  simple  emulsions  to  be  expanded  to  include  his 
beUefs  regarding  the  biological  behavior  of  the  fat  in  living  cells.  We  long 
ago  gave  up  the  notion  of  lipoid  membranes  about  cells  and  the  complex 
notions  of  their  changing  permeability  to  which  Clowes  and  many  authors 
still  hold. 


ON   THE   MAKING  OF  EMULSIONS 


31 


§4. 

To  test  the  view  that  it  is  really  only  the  use  of  a  hydro- 
philic  colloid,  and  this  in  sufficient  amount  to  bind  all  the 
water,  that  makes  possible  the  preparation  of  a  lasting 
emulsion,  other  colloids  may  be  used  in  place  of  acacia. 
By  the  method  outlined  above,  we  have  been  able  to  make 
lasting  emulsions  with  blood  albumin,  egg  white  and  egg 
yolk  (which  in  itself  already  represents  an  emulsion  of  oil  in 
a  hydra  ted  protein  colloid).  We  have  also  succeeded  in 
preparing  lasting  emulsions  by  using  aleuronat  or  casein  as 
the  hydra  ted  colloid.  If  the  temperature  is  properly  con- 
trolled, gelatin  may  be  used. 


gjp^:^:--^ 

^\ 

Lu-iS 

L     ^y.^^    ^ 

1  Soap 

r  Acacia  1 

Egg  Yolk  j 

Crude  1 
Casein  J 

JTmumTf 

lEtfe-Wh.rejLiet'r^narl 

I   AlKal: 
^leuronar] 

«» 

n 

Fig.  6. 

Not  only  may  such  proteins  be  used,  but  hydrophilic 
carbohydrates  of  various  kinds  also  serve  well.  To  the 
list  beginning  with  acacia,  we  may  add  starch,  dextrin  (or 
the  dextrinized  starches  used  in  baby  foods)  and,  when  the 
temperatiu-e  is  properly  regulated,  agar.  A  hydrophilic  col- 
loid which  works  exceedingly  well,  and  to  which  we  shall 
have  occasion  to  return  later,  is  soap.  Emulsions  showing 
a  fair  degree  of  permanence  may  also  be  prepared  by  divid- 
ing oil  into  concentrated  (saturated)  cane  sugar  solutions,  or 
glycerin.  The  last  named  emulsions,  however,  tend  to  sep- 
arate slowly  in  the  course  of  days. 

A  photograph  of  a  series  of  permanent  emulsions  prepared 
with  some  of  these  hydrophilic  colloids  is  shown  in  Figure  6. 


32  FATS  AND  FATTY  DEGENERATION 

Reading  from  left  to  right,  the  jars  contain  permanent 
emulsions  of  cottonseed  oil  in  soap,  acacia,  egg  yolk,  casein, 
blood  albimiin,  egg  white,  acid-aleuronat,  alkali-aleuronat, 
dextrin. 

§5. 

The  substances  enumerated  in  the  last  paragraph  as  capa- 
ble of  yielding  hydrated  colloids  into  which  an  oil  may  be 
divided  successfully  do  not  all  act  with  equal  ease.  This  is 
because  they  behave  differently  from  both  quantitative  and 
qualitative  viewpoints,  so  far  as  the  production  of  a  hy- 
drated colloid  is  concerned,  when  they  are  mixed  with 
water.  Acacia,  blood  albumin,  egg  white,  egg  yolk  and 
casein  yield  the  best  results.  These  substances  not  only 
have  the  power  of  taking  up  much  water,  but  they  form 
fairly  viscid  liquids  and,  what  is  of  even  more  importance,  of 
good  tenacity  ^  with  all  amounts  of  water  added  to  them. 
Moreover,  when  the  water  is  added,  they  yield  relatively 
homogenous  liquids  and  this  occurs  whether  only  a  small 
amount  is  added  or  enough  to  make  the  colloid  go  into 
'^  solution.'^  Furthermore,  this  whole  set  of  changes  ac- 
companying the  addition  of  progressively  greater  amounts 
of  water  may,  in  these  particular  substances,  take  place  at 
one  temperature  (room  temperature). 

With  colloids  which  do  not  so  rapidly  and  effectively  im- 
bibe all  the  water  offered  them  and  which  do  not  pass  so 
easily  and  smoothly  from  the  original  viscid  mixtures  when 
small  amounts  of  water  are  present,  to  the  ultimate  liquids 
approximating  true  solutions  in  character,  greater  difficulties 
are  encountered  in  the  preparation  of  stabile  emulsions. 
The  matter  is  illustrated  in  the  case  of  starch  in  which,  even 
after  prolonged  boiling,  the  individual,  greatly  swollen  starch 

1  We  mean  by  this  the  property  of  being  stretched  into  thin  threads  or 
fihns  without  tearing.  The  oil  globules  need  to  be  separated  from  each 
other  by  a  liquid  which,  with  great  covering  capacity,  possesses  also  this 
high  degree  of  cohesiveness.  We  are  at  present  seeking  for  a  method  of 
measuring  the  values  concerned  in  this  problem  in  somewhat  better  fashion 
than  is  done,  for  example,  by  the  ordinary  "finger  test"  or  by  "glue  testing" 
machines. 


ON   THE   MAKING  OF  EMULSIONS  33 

granules  may  still  be  discerned  microscopically  even  when 
a  small  amount  of  starch  has  been  boiled  for  a  long  time  in 
much  water.  Emulsification  in  agar  or  gelatin  also  pre- 
sents certain  difficulties.  Lasting  emulsions  of  oil  in  gelatin 
are  obtainable  only  by  dispersing  the  oil  in  a  gelatin  mix- 
ture of  a  concentration  which  is  just  fluid  at  the  tempera- 
ture at  which  the  experiment  is  carried  out.  If  with  such 
a  gelatin  colloid  the  temperature  is  raised  (and  its  degree 
of  hydration  thereby  decreased)  a  less  permanent  emulsion 
results.  On  the  other  hand,  an  emulsion  of  oil  in  gelatin 
remains  fixed  if  the  mixture  is  chilled  to  below  the  gelation 
point  of  the  gelatin.  The  dextrins  in  their  properties  of 
forming  hydrophilic  colloids  occupy  a  middle  place  between 
acacia,  egg  yolk  or  casein,  on  the  one  hand,  and  starch  and 
gelatin,  on  the  other. 

§6. 

The  importance  of  the  hydrophilic  character  of  the  col- 
loid used  in  the  preparation  or  stabilization  of  an  emulsion 
is  well  illustrated  in  the  case  of  casein.  Neutral  casein  has 
practically  no  power  of  absorbing  water,  hence  it  has  in 
this  form  no  action  in  stabilizing  an  emulsion.  When  alkali 
is  added  to  the  casein,  it  develops  marked  hj^drophilic  prop- 
erties, and  as  these  appear,  the  power  of  the  casein  to 
stabilize  also  becomes  manifest.  While  neutral  casein  with 
water  and  oil  yields  no  emulsion,  alkalinized  casein  does 
so  at  once. 

It  might  now  be  urged  that  the  real  reason  why  the  addi- 
tion of  alkali  in  this  experiment  yields  an  emulsion,  Ues  in 
its  effect  upon  the  oil  (with  a  consequent  production  of 
soap)  rather  than  in  its  action  upon  the  casein.  This  crit- 
icism can  be  met  in  striking  fashion  by  using  acid  instead  of 
alkali.  Acid  has  no  action  upon  fat,  but  when  it  is  added 
to  casein,  the  hydration  capacity  of  the  casein  is  increased 
just  as  when  alkali  is  added.  On  a  priori  grounds  it  was, 
therefore,  to  be  expected  that  the  addition  of  acid  to  a 
casein-water  mixture  would  prove  just  as  effective  in  mak- 


34 


FATS  AND  FATTY  DEGENERATION 


ing  possible  the  emulsification  of  oil  in  it  as  had  previously 
been  noted  in  the  case  of  alkali.  Experiment  shows  this  to 
be  the  case. 

When  to  5  grams  of  dry  casein  in  each  of  three  mortars 
(or  stirring  devices)  there  are  slowly  added,  respectively, 
50  cc.  2V  normal  sodium  hydroxid,  50  cc.  water,  50  cc.  2V 
normal  hydrochloric  acid,  and,  after  sufficient  time  has 
been  permitted  to  allow  the  casein  to  absorb  all  the  water 
it  will,  into  each  are  stirred  75  cc.  of  oil,  the  results  shown 


Fig.  7. 

in  Figure  7  are  obtained.  The  mixture  of  the  oil  with  the 
hydrated  (alkali)  casein  in  the  jar  on  the  left  has  yielded  a 
perfect  and  permanent  emulsion  and  the  same  result  is 
observable  in  the  case  of  the  hydrated  (acid)  casein  in  the 
jar  on  the  right.  The  middle  jar  shows  an  upper  two- 
thirds  of  almost  clear  oil,  below  this  a  milky  liquid  contain- 
ing microscopically  visible  particles  of  casein  and  fine  oil 
droplets,  and  at  the  bottom  a  white  layer  of  settled  casein. 
The  importance  of  the  hydrophilic  properties  of  the  col- 
loid used  in  stabilizing  a  division  of  oil  in  water  can  often  be 


ON  THE  MAKING  OF  EMULSIONS  35 

noted  in  a  given  mixture  from  which  one  is  trying  to  make  an 
emulsion.  The  addition  of  acid  or  alkali  does  not  at  once 
change  the  previously  neutral  casein  of  a  given  oil-water- 
casein  mixture  into  the  hydrated  form  and  so  one  may  not 
at  once,  with  grinding  in  a  mortar  or  stirring,  succeed  in 
getting  an  emulsion.  Even  an  hour  or  two  may  not  yield  a 
good  result.  But  if  the  mixture  is  simply  left  to  itself  for 
a  while  (as  over  night)  the  first  stroke  of  the  pestle  suffices 
to  start  excellent  emulsification.  In  the  time  allowed,  the 
alkali  or  acid  has  acted  upon  the  protein  and  the  resulting 
compound,  with  its  development  of  hydrophilic  charac^t er- 
istics, has  absorbed  the  ''free"  water  previously  present  in 
the  mixture.  And  as  there  is  substituted  for  the  originally 
tetraphasic  system  of 

oil  :  water  :  casein  :  alkali 
the  diphasic  one  of 

oil  :  hydrated-alkali-casein, 
permanent  emulsification  becomes  easy. 

§7. 

Either  alkali-  or  acid-casein  emulsions  may  be  used  to 
prove  that  emulsification  in  the  protein  is  possible  only  as 
this  contains  a  certain  lower  limit  of  water  or  does  not 
exceed  an  upper  limit. ^  When  mixtures  of  unit  amounts  of 
casein  and  unit  amounts  of  acid  or  of  alkali  have  succes- 
sively greater  amounts  of  water  added  to  them,  emulsifica- 
tion upon  the  addition  of  unit  volumes  of  oil  does  not  begin 
until  a  certain  value  for  the  water  has  been  exceeded.  The 
first  amounts  of  water  make  the  casein  swell  into  an  ex- 
ceedingly stiff,  gum-like  material.  Not  until  enough  water 
has  been  added  to  give  it  a  syrupy  consistency  (at  which 
time  it  will  be  found  to  stretch  into  long  threads  without 
breaking)  or  even  a  less  viscid  character,  does  the  optimum 
for  emulsification  appear.  When,  on  the  other  hand,  too 
much  water  is  added,  the  properties  of  the  pure  water  again 

1  See  page  22. 


36 


FATS  AND  FATTY  DEGENERATION 


become  prominent  and  then  lasting  emulsification  again 
becomes  difficult  or  impossible.  The  matter  is  illustrated 
in  the  following  experiment. 

Into  each  of  five  mortars  are  introduced  respectively  the 
following  mixtures  of  casein,  sodium  carbonate  and  water. 


I. 

n. 

m 

IV. 

V. 

Casein.  .      .          .    . 

5  gm. 
2cc. 
20  cc. 

4  gm. 
1.6  cc. 
20.4  cc. 

3gm. 

1.2cc. 

20.8  cc. 

2gm. 

0.8  cc. 

21.2  cc. 

1  gm. 

0.4  cc. 

21  6  cc. 

Sodium  carbonate  (Molar) 
Water . 

After  the  mixtures  have  been  allowed  to  stand  for  oome 
hours,  10  cc.  of  oil  are  slowly  stirred  into  each.  In  the  first 
mortar  no  emulsification  at  all  is  obtainable ;  in  the  second, 
a  partial  result  is  obtained;  the  third  mortar  gives  a  fairly 
good  emulsion  and  the  fourth  a  perfect  one.  In  the  fifth 
mortar  only  a  coarse,  but  fairly  stabile,  division  of  the  oil 
in  the  hydrated  colloid  is  obtainable. 

These  experimental  results  will  serve  to  emphasize  again 
that  there  exists  a  difference  between  the  possibility  of  pro- 
ducing an  emulsion  in  a  given  alkali-casein  (or  other  hy- 
drated colloid)  and  its  maintenance}  When,  for  example, 
oil  is  being  ground  or  stirred  into  the  hydrated  casein,  an 
optimum  concentration  can  be  discovered  in  which  this  grind- 
ing or  stirring  proves  most  effective  in  subdividing  the  oil. 
As  has  been  noted  by  different  authors,  the  emulsification 
process  is  then  likely  to  emit  a  characteristic  crackling 
sound.  In  other  words,  for  the  production  of  the  emulsion 
certain  optimal  mechanical  conditions  are  required.  On  the 
other  hand,  when  once  a  good  emulsification  has  been  thus 
obtained,  heavy  further  dilution  with  water  will  not  break  the 
emulsion,  even  though  in  such  a  dilute  colloid  medium  the 
emulsification  could  not  have  been  successfully  produced 
in  the  first  place.  ^ 

^  See  page  26. 

2  See  in  this  connection  page  108  on  the  making  of  milks. 


ON  THE  MAKING  OF  EMULSIONS  37 

§8. 

Soap  has  long  served  as  one  of  the  best  of  materials  with 
which  to  favor  the  stabilization  of  a  finely  divided  oil  in 
water.  In  confirming  this  well-known  fact  through  our 
own  experiments  we  should  like  to  emphasize  that  the 
action  of  the  soap  is  probably  decidedly  simpler  than  is 
generally  assumed.  To  permit  the  formation  of  a  permanent 
emulsion,  a  definite  and  rather  high  concentration  of  soap 
must  be  used.  Let  it  be  noted  that  soap  in  such  concen- 
trated form  is  a  typical  hydrophiUc  colloid.  The  forma- 
tion of  an  emulsion  by  dividing  oil  into  such  soap  is  again 
merely  the  process  of  dividing  oil  into  a  hydrated  colloid. 

What  was  said  above  regarding  the  concentration  of  the 
water  in  the  acid-  or  alkali-casein  holds  also  for  soap  when 
thus  viewed  as  the  hydratable  colloid.  Oil  cannot  be  suc- 
cessfully divided  into  a  soap  of  too  nigh  concentration  like 
the  stiff  potassium  soap  which  comes  to  us  in  the  market 
as  the  ordinary  ''soft  soap."  More  dilute  " solutions''  of 
this  soap  work  much  better.  On  the  other  hand,  too  dilute 
solutions  also  fail  not  only  in  the  successful  production  of 
an  emulsion  but  in  the  stabilization  of  the  emulsion  after 
this  has  been  formed.  This  is  easily  seen  in  such  a  series  of 
experiments  as  is  photographed  in  Figure  8.  Each  of  the 
mixtures  contains  water  (20  cc.)  and  oil  (120  cc).  The 
first  cylinder  on  the  left  contains  water  and  oil  only.  The 
remaining  vessels  contain  the  same  amounts  of  water  and 
oil;  but  before  the  oil  was  beaten  into  it,  there  were  added 
to  the  water  different  amounts  of  soap  so  that  the  resulting 
soap-waters  had  the  successive  concentrations  from  left  to 
right  of  0.625,  1.25,  1.875  and  2.5  percent.  When  first 
poured  into  the  jars  shown  in  the  illustration,  after  an 
hour's  beating  in  the  stirring  apparatus,  the  mixtures  look 
much  alike.  The  pure  water  and  oil  mixture  separates 
very  quickly.  In  the  course  of  the  next  48  to  56  hours, 
separation  occurs  in  some  of  the  others.  The  photograph 
was  taken  at  the  end  of  several  days.     Separation  in  the 


38 


FATS  AND  FATTY  DEGENERATION 


first  cylinder  on  the  left,  containing  oil  and  water  only,  is 
practically  complete;  the  same  is  true  for  the  second,  con- 
taining but  little  soap,  and  for  the  third,  which  is  partially 
broken;  the  fourth  cylinder  showed  separation  after  sev- 
eral days,  while  the  fifth  yielded  an  entirely  permanent 
emulsion. 

But  the  soaps  tend  to  lose  their  hydrophilic  properties 
on  mere  dilution.     In  keeping  with  this  fact,  an  increasing 


Fig.  8. 


difficulty  is  noted  in  the  production  of  an  emulsion  as  the 
soap  is  diluted.  Lasting  emulsions  cannot  be  prepared  in 
a  soap  water  below  a  certain  concentration;  more  techni- 
cally put,  enough  hydrophilic  colloid  must  be  present  to 
take  up  all  the  water  as  a  hydrate  before  stabilization  is 
obtained. 

These  facts  make  it  clear,  therefore,  that  for  the  staMliza" 
tion  of  an  emulsion^  there  exists  an  optimum  in  a  region  of 
medium  concentration  of  any  hydrophilic  colloid  —  it  must 
be  neither  too  concentrated  nor  too  dilute.     We  emphasize 


ON  THE  MAKING  OF  EMULSIONS  39 

the  matter  here  because  of  the  biological  appHcations  that 
are  to  be  made  of  it  later.  It  is  in  these  middle  concentra- 
tions that  the  soap  (or  other  colloid)  shows  its  greatest 
covering  power  with  a  high  degree  of  cohesiveness.  In 
other  words,  the  hydrated  colloid  may  here  be  stretched  to 
the  greatest  possible  degree  without  rupture. 

Another  fact  which  it  is  of  great  interest  to  note  at  this 
time  is  the  composition  of  the  various  layers  which  are 
formed  whenever  (as  in  the  second  jar  from  the  left  in  Fig- 
ure 8)  separation  occurs  for  any  reason.  Four  layers  are 
clearly  visible.  Uppermost  is  a  layer  of  pure  oil  which 
shows  black  in  the  photograph;  below  this  comes  a 
second  (white)  oil  layer  containing  a  fine  dispersion  of 
the  aqueous  (soap- water)  phase;  next  comes  soap- water 
containing  a  fine  dispersion  of  oil;  at  the  bottom  is  (prac- 
tically) pure  soap-water.  Each  of  the  two  main  divisions 
of  oil  and  soap-water,  therefore,  remains  contaminated  for 
a  long  time  with  a  small  amount  of  the  opposite  phase. 

§9. 

It  is  of  interest  next  to  consider  the  effects  of  beating 


Fig.  9. 


different  amounts  of  oil  into  a  given  quantity  of  soap  solu- 
tion  of   known   concentration.     The   effect   with   smaller 


40  FATS  AND  FATTY   DEGENERATION 

amounts  of  added  oil  is  shown  in  Figure  9.  Each  of  the 
jars  in  which  the  emulsions  were  prepared  contained  origi- 
nally 25  cc.  of  25  percent  potassium  soap  and  into  them 
were  stirred,  in  slow  successive  additions,  larger  and  larger 
quantities  of  cottonseed  oil.  In  the  five  bottles  of  Figure  9 
are  shown  the  effects  when  20,  30,  40,  50  and  60  cc.  of  the 
oil  are  added.  The  jars  were  photographed  after  they  had 
stood  some  24  hours  following  the  mixing.  Permanent 
emulsification  has  occurred  in  all,  but,  as  clearly  evident, 
the  oil  droplets  still  rise  like  a  cream  to  the  surface  in  the 
first  four  of  the  jars.  It  requires  some  60  cc.  of  oil  before 
the  soap  is  used  up  sufficiently  to  prevent  its  sUpping  to  the 
bottom  from  between  the  oil  droplets. 


Fig.  10. 

The  point  to  be  particularly  emphasized  in  connection 
with  the  experiments  partially  illustrated  in  this  photo- 
graph is  that  the  viscosity  of  the  different  emulsions  also  rises 
from  left  to  right.  Much  greater  quantities  of  oil  can  be 
beaten  into  the  amount  and  concentration  of  soap  chosen 
for  this  series.  As  this  is  done,  the  resulting  emulsion 
becomes  progressively  stiffer  until  finally  it  will  no  longer 
flow.  The  jar  may  then  be  turned  upside  down  without 
the  contents  flowing  out.  Such  a  high  viscosity  is  obtained 
when,  to  the  standard  amount  and  concentration  of  soap, 
150  cc.  or  more  of  oil  are  added.  The  great  viscosity  of 
the  resulting  mixtures  is  graphically  demonstrated  in  Fig- 
ure 10.    These  emulsions  with  their  high  oil  content  can 


ON  THE  MAKING  OF  EMULSIONS  41 

not  only  be  partially  moulded  and  hold  the  shapes  given 
them,  but  a  metal  wire  thrust  vertically  into  each  will 
remain  in  an  upright  position. 

With  still  further  additions  of  oil,  a  critical  point  is 
finally  reached  beyond  which  no  more  oil  can  be  divided 
into  the  soap.  If  the  attempt  is  made  to  do  so,  the  oil  is 
seen  to  separate  out  and  the  whole  mixture  to  go  over  into  the 
second  type  of  emulsion,  namely,  one  of  soap  ivater-in-oil. 
Under  the  conditions  of  our  experiments,  the  transition 
point  is  reached  when  about  470  cc.  of  oil  are  beaten  into 
25  cc.  of  soap  solution.  As  the  oil  separates,  the  viscosity 
of  the  mixture  falls,  resulting  in  a  fluidity  more  nearly  that 
of  oil  itself. 

§10. 

Because  of  the  biological  applications  that  will  subse- 
quently be  made  of  them,  it  is  of  interest  to  study  the 
microscopic  appearances  of  these  emulsions.  The  failure 
to  satisfy  the  mechanical  requirements  previously  discussed 
makes  it  hard  to  get  more  than  a  coarse  emulsion  when  oil 
is  beaten  into  a  relatively  large  amoimt  of  soap  solution. 
This  is  shown  in  Figure  11  which  is  a  photo-micrograph  of 
a  drop  of  the  emulsion  containing  20  cc.  of  oil  and  shown 
in  the  left-hand  jar  of  Figure  9.  Figure  12  shows  a  closer 
packing  of  the  oil  droplets  with  less  free  hydrated-soap 
between  them.  This  is  a  preparation  taken  from  the  emul- 
sion containing  60  cc.  of  oil  and  shown  on  the  extreme 
right  of  Figure  9.  When  optimal  conditions  for  the  divi- 
sion of  the  oil  in  the  soap  are  offered  (as  with  still  higher 
additions  of  oil),  the  oil  droplets  become  so  fine  that  they 
appear  as  mere  granules,  even  when  magnified  many  hun- 
dreds of  times.  Figiu-e  13,  showing  an  approximation  to 
this  state,  is  taken  from  a  mixture  of  300  cc.  of  oil  in  25  cc. 
of  25  percent  soap.  When  oil  is  added  to  the  breaking 
point,  the  picture  shown  in  Figure  14  appears,  in  which 
streaks  of  clear  oil  are  seen  between  the  islands  of  oil-in- 
soap  emulsion. 


42 


FATS   AND  FATTY   DEGENERATION 


Fig.  11. 


Fig.  12. 


ON  THE  MAKING  OF  EMULSIONS 


43 


Fig.  13. 


Fig.  14. 


44         FATS  AND  FATTY  DEGENERATION 

§11. 

The  behavior  of  saturated  cane  sugar  solutions  and  of 
glycerin  deserves  comment.  While  the  great  viscosity  of 
these  solutions  comes  to  mind  as  the  first  element  deter- 
mining the  stability  of  emulsions  prepared  from  them,  it 
must  not  be  forgotten  that  both  are  possessed  of  properties 
indicative  of  a  certain  degree  of  coUoidality.  Not  only 
does  their  viscosity  by  itself  indicate  this,  but,  as  is  well 
known,  these  substances  show  the  Tyndall  phenomenon. 


III.  ON  THE   BREAKING  OF  EMULSIONS. 


III.   ON  THE  BREAKING  OF  EMULSIONS. 
1.   THE   GENERAL  RULE. 

After  what  has  been  written  above  regarding  the  making 
and  the  maintenance  of  emulsions,  we  can  be  brief  regarding 
the  means  by  which  they  may  be  broken.  An  emulsion 
breaks  whenever  the  hydrophilic  (lyophilic)  colloid  which  holds 
the  aqueous  dispersion  medium  is  either  diluied  beyond  the 
point  where  it  can  take  up  the  added  water,  or  is  so  influenced 
by  external  conditions  that  its  original  capacity  for  holding  the 
aqueous  dispersion  medium  is  suffidenMy  reduced.  After 
these  fundamental  conditions  have  been  estabhshed,  certain 
accessory  requirements,  which  will  be  touched  upon  imme- 
diately, must  also  be  satisfied  in  order  that  the  breaking 
may  occur,  but  they  are,  on  the  whole,  of  a  minor  character. 

2.  ILLUSTRATIVE  EXPERIMENTS. 

§1. 
The  fact  that  simple  dilution  will  serve  to  break  an 
emulsion  is  best  illustrated  in  those  cases  in  which  the 
hydrophihc  (lyophihc)  colloid  is  readily  ''soluble"  in  the 
water  (or  other  pure  dispersion  medium).  Soap  emulsions 
or  certain  protein  emulsions,  therefore,  work  best  in  this 
regard.  In  making  the  dilution,  care  must  be  taken  really 
to  wash  the  oil  globules  by  thoroughly  mixing  the  emulsion 
with  the  pure  dispersion  medium.  The  oil  globules  then 
rise  to  the  surface  and  coalesce  to  form  a  continuous  oil 
layer.  In  Figure  15  is  shown  the  effect  of  simply  adding 
water  to  what  was  originally  a  perfectly  stabile  oil-in-soap 
emulsion.  The  first  bottle  on  the  left  contains  the  unit 
quantity  of  standard  oil-in-soap  emulsion  (120  cc.  oil  in 
20  cc.  7  percent  potassium  soap).     The  remaining  bottles 

47 


48         FATS  AND  FATTY  DEGENERATION 

contain  the  same  amounts  of  emulsion  to  which  have  been 
added  successively  larger  amounts  of  distilled  water.     The 


Fig.  15. 

photograph  was  made  48  hours  later.  As  clearly  evident, 
the  addition  of  enough  water  led  to  breaking,  as  illustrated 
in  the  two  bottles  on  the  right  of  the  photograph. 

§2. 

The  breaking  of  an  emulsion  is  also  easily  accomplished 
through  the  addition  of  those  substances  which  destroy  or 
dehydrate  the  hydrophilic  colloids  that  give  an  emulsion  its 
original  stability.  The  substances  that  will  prove  effective 
in  this  regard  are,  of  course,  many  and  different,  depending 
upon  the  nature  of  the  hydrophilic  colloid.  An  illustrative 
series  covering  oil-in-soap  emulsions  is  shown  in  Figure  16. 


ON  THE  BREAKING  OF  EMULSIONS 


49 


The  first  bottle  on  the  left  shows  the  unbroken  (control) 
emulsion.  As  was  to  be  expected,  an  oil-in-soap  emulsion  is 
readily  broken  by  acids,  as  shown  in  the  second  bottle  from 
the  left  of  Figure  16.  The  added  acid  combines  with  the 
base  of  the  soap  and  liberates  its  fatty  acids.  Since  neither 
of  the  products  thus  formed  has  the  marked  hydrophilic 
properties  of  the  original  soap,  the  water  originally  held  as 
a  hA^drate  is  freed.     A  rapid  separation  of  the  emulsion 


Fig.  16. 


follows,  for,  as  we  noted  before,  not  more  than  a  fraction 
of  one  percent  of  oil  can  be  permanently  emulsified  in  pure 
water. 

The  addition  of  an  equal  amoimt  of  alkaU  in  the  form 
of  potassium  or  even  sodium  hydroxid  is  without  effect 
in  bringing  about  a  breaking  of  the  emulsion.  This  is 
shown  in  the  third  bottle.  Yet  if  the  same  amount  of 
alkali  is  added  as  calcium  hydroxid  the  emulsion  separates. 
The  explanation  of  this  fact,  which  is  illustrated  in  the 
fourth  bottle  of  Figure  16,  is  as  follows.  The  soaps  of 
potassium,  sodium  and  calcium  possess  hydrophiUc  prop- 


50         FATS  AND  FATTY  DEGENERATION 

erties  in  very  unequal  degrees.  Potassium  soap  can  hold 
so  much  water  that  it  remains  a  ''soft"  soap  under  ordinary 
circumstances.  Sodium  soap  has  also  the  power  of  ab- 
sorbing much  water,  though  markedly  less  than  potassium 
soap.  Sodium  soap  is  therefore  the  ordinary  soap  of  com- 
merce. Calcium  soap  holds  so  little  water  that  we  cannot 
wash  with  it.  When  to  an  emulsion  of  oil  in  potassium 
soap  we  add  potassium  hydroxid,  nothing  happens.  Even 
when  we  add  sodium  hydroxid,  the  new  sodium  soap  formed 
may  still  hold  enough  water  to  yield  the  hydrated  colloid 
in  which  alone  the  subdivided  oil  may  be  stabilized.  But 
when  we  add  calciimi  hydroxid,  the  resultant  calcium  soap 
holds  so  little  water  that  ''free"  water  appears  in  the 
emulsion  and  so  the  oil  droplets  begin  to  run  together. 

The  hydrophilic  properties  of  potassium  soap  may  be 
reduced  not  only  by  making  some  other  soap  out  of  it,  but 
through  the  addition  of  sufficient  amounts  of  different  salts. 
The  addition  of  enough  salt,  therefore,  is  likely  to  lead  to 
separation  in  an  oil-in-soap  emulsion.  The  fifth  and  sixth 
bottles  from  the  left  in  Figure  16  will  serve  to  illustrate  the 
matter.  To  the  fifth  bottle,  calcium  chlorid  was  added; 
to  the  sixth,  sodium  chlorid. 

The  effect  of  the  anesthetics  alcohol,  chloroform  and 
ether  upon  oil-in-soap  emulsions  is  not  without  interest. 
Alcohol  brings  about  a  rapid  separation  of  the  phases.  The 
soap  dissolves  in  the  alcohol,  but  at  the  same  time  loses  its 
lyophiUc  properties.  The  water  is,  in  other  words,  sepa- 
rated from  its  colloid  combination,  and  as  this  occurs,  the 
oil  droplets  begin  to  flow  together  and  to  separate  out  in 
gross  form.  Chloroform  has  much  the  same  effect  when 
enough  is  used  and  leads  ultimately  to  a  slow  breaking  of 
the  emulsion.  A  fact  not  without  interest  for  our  further 
discussion  is  that  ether  has  hardly  any  effect  in  this  direction. 

The  effects  of  these  three  fat  solvents  are  shown  in  the 
three  bottles  on  the  right  of  Figure  16.  While  we  would 
not  be  understood  as  finding  in  this  behavior  a  complete 
explanation  of  the  relative  toxicity  of  these  different  sub- 


ON  THE  BREAKING  OF  EMULSIONS  51 

stances  when  used  as  anesthetics  upon  living  protoplasm, 
it  is  of  interest  to  note  that  the  order  of  their  action  upon 
these  emulsions  does  parallel  clinical  experience. 

In  the  case  of  an  emulsion  of  oil  stabihzed  in  alkah-casein, 
the  addition  of  a  Httle  acid  breaks  the  emulsion;  while 
alkali  proves  effective  in  this  regard  if  acid-casein  has  been 
used  in  making  the  emulsion.  As  noted  several  years  ago/ 
various  salts  —  even  the  neutral  salts  —  exert  a  dehydrat- 
ing effect  upon  a  protein  hydrated  through  the  presence  of 
an  acid  or  an  alkah.  The  salts  that  are  active  in  this 
regard  act  in  identical  fashion  both  from  a  quantitative 
and  a  qualitative  point  of  view  when  added  to  these  emul- 
sions, breaking  them  whenever  they  bring  about  a  requisite 
degree  of  protein  dehydration  with  the  separation  of  water 
in  '^free'^  form.  Ether,  chloroform  and  alcohol  all  tend  to 
break  emulsions  of  oil  stabihzed  in  protein  and  about  in 
the  order  given,  the  first  named  acting  most  powerfully. 
There  might  at  first  sight  seem  to  be  something  contra- 
dictory between  these  facts  and  those  mentioned  in  the 
previous  paragraph  together  with  the  biological  analogies 
to  the  phenomena  of  anesthesia.  This,  however,  is  not  the 
case.  We  speak  here  of  certain  gross  physical  and  direct 
effects  which  the  anesthetics  have  upon  just  such  emulsions 
as  we  shall  see  later  exist  in  our  tissues.  But  in  Uving 
animals  the  anesthetics  also  have  indirect  effects.  For  ex- 
ample, they  lead  to  an  abnormal  production  and  accumu- 
lation of  acids  in  the  body  —  a  problem  which  Evarts 
Graham  ^  has  recently  studied  to  splendid  advantage  — 
and  these  acids  then  produce  secondary  physico-chemical 
and  biological  effects  which  entirely  obscure  the  primary 
physical  effect  under  discussion  here. 

The  emulsions  hardest  to  break  are  those  in  which  the 


1  See  Martin  H.  Fischer  and  Gertrude  Moore:  Am.  Jour.  Physiol., 
20,  330  (1907);  Pfluger's  Arch.,  124,  69  (1908);  ibid.,  125,  99  (1908);  see 
also,  Martin  H.  Fischer:  (Edema  and  Nephritis,  2nd  edition,  46,  New 
York,  1915. 

2  Evarts  Graham:  Jour.  Exp.  Med.,  22,  48  (1915). 


52         FATS  AND  FATTY  DEGENERATION 

carbohydrates  like  acacia,  dextrin  or  starch  have  been  used 
to  produce  the  stabilization.  Acids  or  alkalies  in  moderate 
concentrations  are  without  effect  upon  them.  This  is  be- 
cause in  the  concentrations  used,  these  materials  have 
practically  no  action  upon  these  carbohydrate  hydration 
compounds.  The  same  may  be  said  regarding  the  effects 
of  salts,  alcohol,  chloroform  or  ether,  which  in  other  emul- 
sions produce  such  marked  effects.  The  emulsions  stand, 
therefore,  in  spite  of  the  addition  of  these  various  sub- 
stances. 

This  great  stabihzing  effect  of  the  colloid  carbohydrates 
will  also  aid  us,  we  believe,  in  the  understanding  of  certain 
problems  associated  with  the  anesthetics  and  with  the 
effects  of  other  poisons  in  the  body.  The  tissues  are  less 
easily  poisoned  by  the  anesthetics,  for  instance,  when  gly- 
cogen is  present  in  the  cells.  In  trying  to  explain  this  fact, 
it  is  well  to  remember  that  the  presence  of  this  colloid  car- 
bohydrate and  of  other  carbohydrates  like  it  tends  to  sta- 
bihze  oil-in-protein  and  oil-in-soap  emulsions  against  the 
effects  of  various  added  substances  which  would  otherwise 
destroy  the  emulsions. 

§3. 

To  this  list  of  the  methods  by  which  an  emulsion  may  be 
broken  should  be  added  the  effects  of  mere  drying.  Just  as 
oil  cannot  be  divided  into  a  hydrated  colloid  until  this  has 
come  to  contain  a  certain  minimum  of  water,  just  so  the 
resultant  emulsion  will  separate  again  if,  after  it  is  prepared, 
the  water  is  allowed  to  evaporate  from  it.  This  may  be 
observed  very  well  in  oil-in-soap  emulsions  or  oil-in-hydrated 
protein  emulsions  which  separate  into  oil  and  concentrated 
colloid  residues  as  soon  as  they  are  permitted  to  dry  suffi- 
ciently. 


ON  THE  BREAKING  OF  EMULSIONS  53 

3.   SPECIAL  CONSIDERATIONS. 

A  final  word  should  be  added  regarding  certain  accessory 
conditions  which  need  to  be  satisfied  in  order  to  accomplish 
the  breaking  of  an  emulsion.  In  order  that  the  oil  droplets 
may  coalesce,  thoy  must  be  brought  into  physical  contact 
with  each  other.  For  this  reason,  emulsions  containing  a 
high  concentration  of  oil  tend  to  break  more  easily,  more 
quickly,  and  more  perfectly  than  less  concentrated  ones. 
Very  dilute  emulsions  tend  to  hold  for  long  periods  of  time. 
Coarsely  divided  oil  particles,  moreover,  coalesce  more 
easily  than  do  those  more  finely  divided. 

Following  the  general  laws  governing  the  distribution  of 
a  third  material  between  two  phases,  an  emulsion  will  fre- 
quently stand  heavy  dilution  with  water  or  the  addition  of 
materials  which  dehydrate  the  stabiHzing  colloid  without 
breaking,  if  the  colloid  material  either  is  from  the  first,  or 
comes  to  be,  concentrated  in  the  surface  between  the  oil 
globules  and  the  aqueous  phase.^  This  is  why  oil-in-pro- 
tein  emulsions  (the  milks,  for  example) ,  resist  the  addition 
of  water  and  will  not  break  easily  even  when  powerful  de- 
hydrating agents  are  added  to  them.  It  also  explains  why 
the  addition  of  suspension  colloids  or  their  production  (as 
in  the  case  of  the  finely  divided  metals)  in  an  oil-water  mix- 
ture gives  the  emulsion  a  fair  stability.  Through  such 
adsorption  effects  and  the  protecting  films  thereby  drawn 
over  the  oil  globules,  these  may  be  kept  from  coalescing 
even  though  every  other  opportunity  is  offered  them  to  do 
so.  It  is  only  for  this  reason  that  dilution  alone  does  not 
sufl&ce  to  break  every  emulsion. 

1  See  in  this  connection  S.  U.  Pickering:  Kolloid-Zeitschrift,  7,  15  (1910). 


IV.   ON  THE  NORMAL  FAT  CONTENT  OF  CELLS. 


IV.   ON  THE  NORMAL  FAT  CONTENT  OF  CELLS. 

1.   THE   GENERAL  FACTS. 

We  are  now  in  a  position  to  use  the  experiments  on  emul- 
sions detailed  in  the  previous  sections  for  the  interpreta- 
tion of  certain  of  the  problems  associated  with  the  history 
of  fat  in  biological  material. 

It  may  be  stated  as  generally  true  that  all  cells  and 
fluids  of  the  body  contain  fat  and  fat-like  substances.  The 
amount  that  they  contain  varies  greatly  not  only  in  a  given 
cell  or  body  fluid  under  difi'erent  physiological  or  patho- 
logical circumstances,  but  at  all  times  in  the  difi'erent  cells 
and  fluids.  Certain  of  the  body  cells,  for  example,  contain 
at  no  time  more  than  slight  amounts,  while  others  may 
show  the  enormous  values  characteristic  of  the  adipose 
tissues.  But  even  the  slight  amoimts  found  in  fat-poor  cells 
or  body  fluids  suffice  to  raise  the  biologically  important 
question  of  how  even  these  may  be  and  are  carried. 

In  order  to  obtain  a  first  and  rough  insight  into  the  whole 
problem,  let  us  view  the  classic  figures  of  E.  Bischoff.^  In 
his  chemical  analysis  of  a  thirty-three  year  old  man,  he 
found  the  body  as  a  whole  to  contain  58.5  percent  water, 
18  percent  fat  and  about  20  percent  protein.  From  this 
total  fat  figure  we  shall  subtract  one-half,  or  even  two- 
thirds,  as  contained  in  the  readily  separable  adipose  tissues 
of  the  body.  The  question  of  the  fat  in  these  tissues  re- 
ceives individual  study  later.^  But  even  after  we  have 
made  this  liberal  subtraction,  several  percent  (and  these 
calculated  in  terms  of  the  moist  weight  of  the  body)  still 
remain  hidden  in  discrete  form  in  the  rest  of  the  tissues 

1  E.  Bischoff:  Vierordt's  Daten  imd  Tabellen,  187,  Jena,  1888. 
*  See  page  89. 

57 


58 


FATS  AND   FATTY   DEGENERATION 


and  fluids  of  the  body.     By  what  means  is  this  made 
possible? 

As  a  matter  of  fact,  the  problem  is  not  as  simple  as  these 
average  figures  would  seem  to  indicate;  when  for  these 
there  are  substituted  those  actually  observed  in  the  analysis 
of  individual  organs,  it  is  found  that  the  fat  content,  instead 
of  amounting  to  a  few  percent,  rises,  in  some  instances,  to 
a  quarter  of  the  total  moist  weight  of  the  cells.  Table  I, 
taken  from  Gorup-Besanez,^  illustrates  this.  The  values 
are  in  nearly  all  cases  too  low,  for  they  date  from  a  time 
when  the  better  methods  of  fat  analysis  now  available  were 
unknown. 


TABLE  I. 
Percentage  of  Fat  in  Different  Fluids  and  Organs  of  the  Body. 


Sweat 

0.001 

0.002 

0.02 

0.05 

0.06 

0.06 

0.2 

0.3 

0.4 

1.4 

4.3 

Cartilage 

1  3 

Vitreous  humor 

Bone  

1  4 

Saliva 

Crystalline  lens 

2  0 

Lymph 

Liver 

2  4 

Synovial  fluid 

Muscle 

3  3 

Amniotic  fluid 

Hair     

4  2 

Chyle 

Brain  

8  0 

Mucus 

Nerve 

22  1 

Blood   . . 

Bile 

Milk 

1  Gorup-Besanez:    Quoted  by  W.    D.    Halliburton,    Schafer's    Text- 
Book  of  Physiology,  1,  17,  Edinburgh,  1898. 


ON  THE  NORMAL  FAT  CONTENT  OF  CELLS 


59 


Table  II  may  be  added  in  illustration  of  further  analyses 
in  this  direction. 


TABLE  II. 
Percentage  Composition  of  Different  Body  Fluids  and  Tissues. 


Dog  serum  ^ 

Dog  chyle  ^ 

Dog  chyle. 

Synovial  fluid  ^ 

Lens  * 

Rabbit  muscle 

Prairie  chicken  muscle. 

Human  muscle  ^ 

Animal  retinas  * 

Leucocytes' 

Calf  thymus 

Ox  thymus 

Fresh  bone" 

Veal  liver  ^2 

Egg  yolk  ^3 


Water.        Fat  and  Lipoid. 


93.60 
90.67 


93.08 
63.50 
75. 10 5 

is.'so 

86  to  90 
88.51 


50.00 
47!i9 


0.68 

6.48 
.25  to  14.6  2 

0.87 

0.74 

1.076 

1.43« 

2  27 
1.27  to  4.13 

2.00 

1.3710 
16.801" 
15.75 

5  30 
35.31 


Protein. 


4.52 
2.10 


5.20 
34.93 
16  to  20 

20.01 
5.71  to  8.45 
8.00 

11.40 
19.00 
15.63 


Ash. 


0.87 
0.79 


0.85 
0.82 

3.12 

0.69  to  1.2 

1.11 

21.85 
1.30 
0.97 


1  F.  Hoppe-Seyler:  Quoted  by  E.  A.  Schafer,  Schafer's  Text-Book  of  Physiology,  1,  183, 
Edinburgh,  1898. 

2  Zawii£ky:  Cited  by  H.  Vierordt,  Daten  und  Tabellen,  154,  Jena,  1888. 

3  Salkowski:  Quoted  by  E,  A.  Schafer,  Schafer's  Text-Book  of  Physiology,  1,  184,  Edin- 
burgh, 1898. 

*  Laptschivskt:  Quoted  by  W.  D.  Halubxtbton,  Schafer's  Text-Book  of  Physiology,  1,  123, 
Edinburgh,  1898. 

5  J.  Ranke:  Quoted  by  Otto  Nasse,  Hermann's  Handbuch  d.  Physiologic,  1,  1  ter  Theil, 
284,  Leipzig,  1879. 

e  J.  KoxiG  and  B.  Farwick:  Quoted  by  Otto  Nasse,  Hermann's  Handbuch  d.  Physiologie, 
1,  1  ter  Theil.  283,  I^ipzig,  1879. 

^  W.  D.  Hallibcrton:   Schafer's  Text-Book  of  Physiology,  1,  95,  Edinburgh,  1898. 

8  Cahn:   F.  Hoppe-Seyler's  Physiol.  Chem.  699,  Berlin,  1881. 

»  Liuenfeld:  Quoted  by  W.  D.  H.\lliburton,  Schafer's  Text-Book  of  Physiology,  1,  82,  Edin- 
burgh, 1898. 

10  Friedleben:    Quoted  by  F.  Hoppe-Seyler,  Physiol.  Chem.  721,  Berlin,  1881. 

"  F.  Hoppe-Seyler:  Quoted  by  W.  D.  Haluburton,  Schafer's  Text-Book  of  Physiology,  1, 
111.  Edinburgh,  1898. 

12  Atwater  and  Bryant:  Quoted  by  W.  H.  Howell,  Text-Book  of  Physiology  938,  6th 
Edition,  Philadelphia,  1915. 

13  Parke:  Quoted  by  F.  Hoppe-Seyler,  Physiol.  Chem.,  782,  Berlin,  1881. 


60 


FATS  AND   FATTY   DEGENERATION 


The  composition  of  some  of  those  tissues  which,  exclusive 
of  the  purely  adipose  tissues,  show  the  highest  figures  in 
the  matter  of  fat  content,  is  emphasized  in  Table  III. 

f  TABLE   III. 

Percentage  Composition  of  Nerve  Tissue. 


Gray-matter  of  ox  brain  (Pe- 
TROWSKY  ^) 

White-matter  of  ox  brain  (Pe- 
TROWSKY  ^) 

Human  spinal  cord 

Human  sciatic  nerve 


Water. 


81.60 

68.35 

74.842 
58.33 4 


Dry 

Matter 


18.40 

31.65 
25.16 
41.67 


Percentage  Composition  of  Dry 
Matter. 


Fat  and 
Lipoid. 


36.45 

71.36 
75.13 
56.09  5 


Pro- 
teins. 


55.37 


Other 
Mate- 
rials. 


6.71 
3.34 


24.73 
23.80 
36.80!  7.07 


Salts 


1.45 

0.57 
1.1 


1  Petrowsky:  Pfluger's  Arch.,  7,  367  (1873). 

2  E.  Bischoff:  Vierordt's  Daten  und  Tabellen,  187,  Jena,  1888. 

'  Moleschott:  Quoted  by  W.  D.  Halliburton,  Schafer's  Text-Book  of  Physiology,  1,  116, 
Edinburgh,  1898. 

*  E.  Bischoff:  Vierordt's  Daten  und  Tabellen,  187,  Jena,  1888. 

5  Josephine  Chevalier:  Quoted  by  W.  D.  Halliburton,  Schafer's  Text-Book  of  Physi- 
ology, 1,  116,  Edinburgh,  1898. 


2.   PROTOPLASM   AS   AN   EMULSION. 

These  three  tables  suffice  to  show  that  even  those  fluids 
and  tissues  of  the  body  which  are  poorest  in  fat  may  already 
show  values  which  lie  beyond  the  limits  of  the  amounts 
that  may  be  ^'dissolved"  or  suspended  permanently  (in 
colloid  form)  in  pure  water.  And  when  the  high  fat  values 
characteristic  of  some  of  the  tissues  are  reached,  the  possi- 
bility of  considering  the  problem  as  identical  with  that  of 
the  mere  division  of  oil  in  water  disappears  entirely. 

The  fats  can  he  held  in  such  high  amounts  in  the  cells  and 
fluids  of  the  body  only  because  they  are  emulsified  in  the  cell 
protoplasm.  Were  the  generally  accepted  notions  correct, 
according  to  which  cells  are  mere  osmotic  bags  made  up  of 
a  surrounding  semipermeable  membrane  within  which  is 
held  an  aqueous  solution  of  salts  and  various  non-electro- 
lytes, it  would  be  impossible  ever  to  find  in  them,  in  per- 
manently subdivided  form,  more  than  a  fraction  of  one 


ON  THE   NORMAL  FAT  CONTEXT  OF  CELLS  61 

percent  of  fat.  The  reason  why  living  cells  are  readily  able 
to  hold  amounts  of  fat  exceeding  these  low  valites  and  even  to 
the  point  where  they  make  up  twenty-five  percent  of  the  total 
(moist)  cell  substance  is  because  the  cells  are  composed  for  the 
most  part  of  hydrophilic  colloids.  As  hydrated  colloids  are 
able  to  stabilize  the  division  of  an  oil  in  an  aqueous  medium, 
just  so  do  the  hydrophilic  proteins,  soaps  and  carbohy- 
drates existing  in  the  tissues  and  their  secretions  make  it 
possible  for  these  to  hold  the  large  amounts  of  fat  found  in 
them  in  permanently  subdivided  form. 

Tables  II  and  III  (as  well  as  the  now  extensive  evidence  ^ 
available  indicating  that  the  dominant  factor  determining 
the  amount  of  water  held  by  protoplasm  under  normal 
and  abnormal  circiunstances  is  found  in  the  colloid  behavior 
of  the  proteins)  show  that  the  most  important  hydrophilic 
colloids  concerned  in  stabilizing  the  normal  fat  content  of 
the  different  tissues  and  fluids  of  the  body,  come  from  the 
class  of  the  proteins.  The  proteins  need  not  and  do  not, 
however,  play  an  exclusive  role  in  this  direction.  Not  only 
is  it  to  be  suspected  that  the  various  hydrophilic  carbo- 
hydrates must  play  some  part  (especially  in  plants),  but  the 
soaps,  so  often  appearing  under  normal  and  abnormal  cir- 
cumstances in  various  cells  and  secretions,  must  also  be 
considered.  The  high  soap  content  of  bile,  for  example, 
may  well  be  the  chief  agent  keeping  the  fats  and  lipoids  so 
constantly  found  in  this  secretion  from  separating  out  in 
gross  form.2  The  analytic  figures  of  B.  Moore  ^  contained 
in  Table  IV  illustrate  the  matter. 

1  See  Martin  H.  Fischer:  Physiology  of  Alimentation,  187  and 267,  New- 
York,  1907;  Am.  Jour.  Physiol.,  20,  330  (1907);  Pfluger's  Arch.,  124,  69  (1908); 
ibid.,  126,  396  (1908);  ibid.,  127,  1  (1909);  ibid.,  127,  46  (1909);  see  also  the 
several  papers  since  in  the  KoUoid-Zeitschrift.  A  running  account  is  found  in 
(Edema  and  Nephritis,  2nd  edition.  New  York,  1915. 

2  The  important  bearing  that  these  considerations  have  upon  the  mecha- 
nism of  gall-stone  formation  (cholesterin  stones,  for  example)  is  self-apparent. 

^  B.  Moore:   Schafer's  Text-Book  of  Physiology,  1,  370,  Edinburgh,  1898. 


62 


FATS  AND  FATTY   DEGENERATION 


TABLE  IV. 
Percentage  CoMPOSITIO^ 

OF  Bile. 

Fats  and 
Lipoids. 

Soap. 

Taurocho- 
lates. 

Mucin. 

Other  Or- 
ganic 
Materials. 

Gall  bladder  bile 

Liver  bile 

5.982 
1.146 

0.527 
0  409 

3.155 
0.104 

0.127 
0.110 

11.959 
12.602 

3.460 
3.402 

0.454 
0.245 

0.053 
0.170 

0.973 
0.274 

0.442 

0.543 

3.   BIOLOGICAL  CONSEQUENCES. 

These  considerations  would  seem  to  compel  the  conclu- 
sion that  under  normal  circumstances  the  fat  found  in  the 
body  cells  and  fluids  is  there  in  finely  divided  form  and  is 
kept  so  through  the  agency  of  various  hydrated  colloids 
(proteins,  carbohydrates  and  soaps).  In  thus  pointing  out 
the  parallelism  existent  between  various  tissues  and  fine 
emulsions,  we  obtain  at  the  same  time  an  understanding  of 
certain  other  phenomena  familiar  from  study  of  biological 
materials. 

§1. 

When  a  yellow  oil,  like  cottonseed  oil,  is  divided  into  a 
practically  colorless  liquid  like  a  soap  or  protein  solution, 
the  mixture  becomes  brilliantly  white.  The  white  color  of 
the  white  matter  of  the  brain,  and  the  whiteness  of  nerve 
tissue,  may  be  regarded  as  expressive  of  the  same  type  of 
subdivision  of  fat  and  lipoid  into  the  hydrated  protein 
(chiefly)  which  makes  up  the  rest  of  these  anatomical  struc- 
tures. 

The  fact,  moreover,  that  even  such  large  amounts  of  fat 
as  may  be  present  in  certain  tissues  (like  those  of  the  brain 
and  peripheral  nerves)  need  not  betray  themselves  optically 
or  to  the  ordinary  fat  stains  like  Sudan  III  and  osmic  acid 
is  also  identical  with  the  behavior  of  such  fine  emulsions  as 
may  be  prepared  experimentally.  Emulsions  may  be  made 
so  fine  that  refraction  effects  no  longer  suffice  to  bring  out 


ON  THE  NORMAL  FAT   CONTENT  OF  CELLS  63 

the  oil  droplets  and  such  staining  methods  fail  to  demon- 
strate the  presence  of  fat. 

§2. 

A  matter  of  biological  importance  for  the  theory  of  cell 
structure  is  contained  in  the  question  of  whether,  normally, 
the  fat  in  a  cell  constitutes  the  divided  phase  and  the  hy- 
drated  colloid  making  up  the  rest  of  the  cell  is  the  contin- 
uous, enveloping  phase,  or  vice  versa.  There  are  several 
proofs  that  the  former  is  decidedly  the  case. 

The  chemistry  of  fat  production  in  cells  is  such,  first  of 
all,  that  the  fat  is  laid  down  in  finely  divided  particles. 
When  fat  is  newly  synthesized  in  the  cells  from  fatty  acid 
and  glycerin,  the  particles  are  originally  of  molecular  di- 
mensions only.  If  the  molecules  of  fat  are  formed  in  a 
hydrated  colloid  (like  the  protoplasm  of  the  normal  cell) 
the  fat  particles  must  tend,  evidently,  to  remain  finely 
divided  unless  something  happens  to  bring  about  their 
coalescence. 

Second,  the  question  of  whether,  upon  mixing  two  im- 
miscible liquids  with  each  other,  we  shall  get  a  subdivision 
of  the  first  in  the  second  or  of  the  second  in  the  first,  is 
governed  to  a  certain  extent  by  the  quantitative  relation- 
ships existing  between  the  two.  Speaking  generally,  oil 
will  tend  to  become  the  disperse  phase  if  Uttle  of  it  is  beaten 
into  much  water,  while  water  will  become  the  disperse 
phase  if  the  quantitative  relationships  are  reversed.  On 
the  basis  of  probability  alone,  therefore,  it  may  be  assumed 
in  advance  that  amoimts  of  fat  up  to  the  values  discussed 
thus  far  (25  percent  of  the  total  weight  of  the  moist  tissue) 
will  go  to  form  the  divided  phase,  while  the  hydrated  col- 
loids making  up  the  rest  of  the  cell  will  form  the  continuous, 
enveloping  one. 

For  a  third  proof  in  this  direction,  we  need  but  point  to 
the  behavior  of  the  body  fluids  and  tissues  discussed  thus 
far  toward  paper,  to  the  feel,  and  toward  admixture  with 
an  aqueous  dispersion  medium  like  water.     Blood,  lymph, 


64  FATS  AND  FATTY  DEGENERATION 

bile,  saliva,  skeletal  muscle,  heart  muscle,  kidney,  spleen, 
fat-free  pancreas,  brain  and  even  nerve,  do  not  ^'oil"  but 
simply  ''wef  a  paper  with  which  they  are  brought  in  con- 
tact. Neither  do  these  materials  impart  an  oily  ''feel" 
when  rubbed  between  the  fingers.  Finally,  all  these  fluids 
or  tissues  may  be  readily  mixed  into  and  with  water. 
They  may,  therefore,  all  be  washed  off  and  out  of  contain- 
ing vessels  as  readily  as  ordinary  milk  or  egg  yolk.  Were 
the  oil  the  external  or  enveloping  phase  none  of  these 
things  would  be  possible.^ 

If  this  simple  logic  is  acquiesced  in,  it  means  further  evi- 
dence (were  such  still  needed  2)  proving  untenable  the  bio- 
logical concept  that  the  cell  is  surrounded  by  a  plasma-film 
of  fat  or  fat-like  materials.  Were  this  concept  correct,  all 
unicellular  organisms  and  all  multicellular  aggregates  (like 
the  tissues)  for  which  such  a  belief  is  supposed  to  be  valid 
should  oil  paper,  feel  oily  and  resist  admixture  with  aqueous 
solutions  as  markedly  as  do  the  pure  fats  and  lipoids  them- 
selves.    This,  obviously,  they  do  not  do. 

1  See  page  89. 

2  See  the  reference  under  Martin  H.  Fischer  cited  on  page  61. 


V.  ON  FATTY  CHANGE   (FATTY  INFILTRATION 
AND  FATTY  DEGENERATION). 


V.   ON  FATTY  CHANGE    (FATTY  INFILTRATION 
AND  FATTY  DEGENERATION). 

1.  HISTORICAL  REMARKS. 

The  problems  of  "fatty  inj&ltration'^  and  ''fatty  degen- 
eration" have  been  much  discussed  since  Rudolph  Vir- 
CHOW^  first  defined  the  terms  in  the  middle  of  the  last 
century.  Under  the  first  term,  Virchow  understood  the 
excessive  deposition  of  fat  in  a  cell;  under  the  second,  a 
change,  pathological  for  the  most  part,  whereby  the  cell 
substance  itself  was  converted  into  fat.  Virchow' s  views 
rested  for  the  most  part  upon  theoretical  conceptions  and 
upon  histological  studies.  Chemical  support  for  them  was 
found  some  twenty  years  later  through  the  work  of  Carl 
VON  VoiT.-  In  the  seventies  of  the  last  century,  this  author 
detailed  experiments  which  tended  to  lift  from  the  realm  of 
speculation  into  that  of  experimental  fact  the  suggestion  of 
Virchow  that  the  proteins  of  the  cell,  for  example,  might 
be  changed  into  fat.  In  his  studies  of  metabolism,  Voit 
beheved  he  had  figures  at  hand  which  showed  that  the 
protein  consumed  by  an  animal  can  be  converted  into  and 
stored  as  fat.  This  behef,  which  held  sway  for  many  years, 
was  made  the  subject  of  trenchant  criticism  by  E.  PrLtJGER* 
and  his  co-workers,  who,  on  the  basis  of  new  analyses  and 
a  recalculation  of  the  figures  cf  Voit,  showed  these  figures 
to  be  inadequate  to  support  his  contention.  At  the  present 
time  it  may  safely  he  asserted  that  while  the  conversion  of 
protein  into  fat  in  the  higher  animals  still  remains  a  theo- 
retical possibility,  no  experiments  exist  which  prove  it;  and 
all  evidence,  as  it  now  stands,  is  entirely  against  it. 

The  hypothesis  of  Virchow,  according  to  which  the  pro- 

1  Rudolph  Virchow:  Virchow's  Arch.,  1,  94  (1847). 

2  Carl  von  Voit:    Zeitschr.  f.  Biol.,  6,  277  (1870);   ibid.,  7,  433  (1871). 
8  E.  Pfluger:   Pfluger's  Arch.,  77,  521  (1899). 

67 


68  FATS  AND  FATTY  DEGENERATION 

tein  of  a  cell  may  be  converted  into  fat,  has  in  these  later 
years  been  gradually  replaced  by  one  which  holds  that  in 
fatty  degeneration  an  excessive  amount  of  fat  simply  be- 
comes deposited  in  the  affected  cells.  The  term  ''fatty 
degeneration"  has,  therefore,  come  to  blend  more  and  more 
with  the  older  one  of  ''fatty  infiltration/^  For  this  view 
G.  RosENFELD^  has  been  chief  sponsor.  Rosenfeld  and 
others  with  him  fed  animals  fat  of  a  composition  different 
from  that  of  their  own  bodies  and  after  having  discovered 
that  the  foreign  fat  is  laid  down  as  such  in  the  fat  depots 
of  the  animals,  these  authors  poisoned  the  animals  with 
substances  known  to  be  capable  of  producing  extensive 
fatty  degeneration  (phosphorus,  chloroform,  alcohol,  phlor- 
izin, etc.).  On  analyzing  the  fat  found  in  the  organs 
which  had  undergone  the  experimentally  produced  fatty 
degeneration,  the  authors  discovered  it  to  be  identical  with 
the  foreign  fat  previously  fed  these  animals.  On  the  basis 
of  these  observations,  Rosenfeld  and  those  of  his  opinion 
hold  that  in  fatty  degeneration  there  merely  occurs,  for 
reasons  as  yet  little  understood,  a  transport  and  increased 
storage  of  the  body  fat  in  the  affected  cells.  In  further 
support  of  their  views  and  against  the  idea  that  some  con- 
stituent of  the  cell  protoplasm  itself  (like  the  protein)  is 
converted  into  fat,  they  adduce  the  fact  that  when  poisons 
known  to  produce  fatty  degeneration  are  given  to  lean 
(fat-free)  animals,  fatty  degeneration  of  the  visceral  organs 
is  not  obtained.  Did  the  fat  of  fatty  degeneration  really 
come  from  the  protoplasm  of  the  cells  themselves,  then 
fatty  degeneration  should  naturally  be  as  easily  obtainable 
in  lean  animals  as  in  fat  ones. 

But  further  study  of  the  subject  has  shown  that  in  fatty 
degeneration  this  abnormally  great  infiltration  with  fat 
neither  needs  to  occiu",  nor  does  occur.  Qitantitative  chem- 
ical analyses  have  gone  to  prove  that  even  in  heavily  degener- 
ated organs  the  amount  of  fat_actuallyJound  in  them  need 

^  G.  Rosenfeld:  Ergebnisse  d.  Physiologic,  1,  Ite  Abth.  651  (1902); 
idid.,  2,  Ite  Abth.  50  (1903). 


ON  FATTY  CHANGE  69 

not  exceed  theirjiorii^^  In  fact,  many  analyses 

are  at  hand  which  show  that  organs  in  fatty  degeneration 
may  contain  less  fat  than  is  normal  for  them.^ 

The  concept  of  fatty  degeneration  is,  therefore,  seen  to 
rest  chiefly  on  purely  histological  (optical)  grounds.  It 
simply  looks  as  though  there  were  more  fat  in  the  affected 
cells.  There  exists  no  chemical  proof  showing  that  fat  is 
produced  from  the  cell  protoplasm;  the  concept  of  an  in- 
creased infiltration  rests  upon  questionable  evidence;  and 
quantitative  study  shows  that  even  such  tissues  as  all 
pathologists  will  agree  to  be  in  a  condition  of  fatty  degen- 
eration may  contain  no  increase  in  amount  of  fat  above 
the  normal  if,  indeed,  they  do  not  show  an  actual  loss. 
The  real  qiiestion  regarding  fatty  degeneration,  therefore,  comes 
to  this:  how  does  a  given  amount  of  fat ,  previously  invisible 
in  a  cell,  become  readily  visible? 

2.    ** FATTY  DEGENERATION"  IN   EMULSIONS. 

It  will  help  toward  a  juster  appraisement  of  some  of  the 
evidence  to  be  offered  later  if  we  first  reproduce  some 
photo-micrographs  of  tissues  in  typical,  fatty  degeneration. 
Sections  of  normal  kidney,  heart  muscle  or  nerve  do  not 
betray  the  presence  of  fat  in  them,  but  when  these  tissues 
have  suffered  a  ''fatty  degeneration"  or  a  ''fatty  infiltra- 
tion'^  (as  judged  on  the  ordinary  basis  of  optical  appear- 
ance), pictures  like  those  shown  in  Figures  17,  18  and  19 
are  obtained.^  As  already  emphasized,  chemical  analysis 
shows  that  the  actual  amounts  of  fat  foimd  in  the  organs 
imder  such  circumstances  need  not  exceed  the  normal 
values,  and  yet  it  is  now  readily  visible  in  the  form  of  gross 
globules  in  all  these  tissues. 

1  G.  Rosenfeld:  Ergebn.  d.  Physiologie,  2,  Ite  Abth.  66  (1903);  also 
G.  Walter:  Virchow's  Arch.,  20,  426  (1861);  A.  E.  Taylor:  Jour.  Exp. 
Med.,  4,  399  (1899);  Jour.  Med.  Research,  9,  59  (1903);  A.  Rosenthal: 
Deut.  Arch.  f.  klin.  Med.,  78,  94  (1903). 

2  Figure  17  is  from  E.  Gierke:  Aschoff's  Path.  Anat.,  1,  322,  Jena,  1909; 
Figures  18  and  19,  from  F.  B.  Mallory:  Pathologic  Histology,  90  and  92, 
Philadelphia,  1914. 


70 


FATS  AND  FATTY  DEGENERATION 


**«^v. 


&<»£ 


^^\m\ 


j^-m^^ 


Fig.  17. 


^^'.Vj:' 


Fig.  18. 


ON  FATTY  CHANGE 


71 


In  keeping  with  our  argument  regarding  the  fat  in  cells, 
as  thus  far  developed,  we  can  only  conclude  that  fatty  de- 
generation represents  merely  a  coarsening  of  the  normal  fine 
emulsion  of  fat-in-protoplasm  to  a  more  readily  trisible  size. 

In  a  previous  section  ^  it  was  pointed  out  that,  depending 


Fig.  19. 

upon  the  nature  of  the  hydrophilic  colloid  used  to  stabilize 
a  fine  emulsion  of  oil  in  an  aqueous  dispersion  medium, 
different  agencies  capable  of  dehydrating  the  hydrophilic 
colloid  may  be  used  to  bring  about  the  separation  of  the 
constituents  of  the  emulsion  in  grosser  form.  It  behooves 
us  now  to  ask  what  is  the  appearance  of  this  separation 
^  See  pages  47  to  51. 


72 


FATS  AND  FATTY  DEGENERATION 


Fig.  20. 


Fig.  21. 


ON  FATTY  CHANGE 


73 


Fig.  22. 


m 


Fig.  23. 


74         FATS  AND  FATTY  DEGENERATION 

when  followed  microscopically.  Figures  20,  21,  22  and  23 
are  introduced  by  way  of  illustration.  Figure  20  is  merely 
the  microscopic  picture  (magnified  some  850  times)  of  a 
rather  fine  emulsion  of  oil  in  soap.  In  Figure  21  is  shown 
the  effect  of  letting  a  drop  of  yo^^  normal  acid  (hydro- 
chloric, lactic,  beta-hydroxy-butyric  or  diacetic)  diffuse  into 
the  emulsion.  As  is  clearly  apparent,  the  destruction  of 
the  hydrophilic  properties  of  the  soap  is  followed  by  a 
coalescence  of  the  oil  droplets  so  that  instead  of  being  in- 
distinguishable as  before,  they  now  become  readily  visible 
in  coarse  form.  Figure  22  shows  the  same  phenomenon,  as 
produced  by  allowing  a  small  amount  of  dilute  alcohol  to 
diffuse  into  the  oil-in-soap  emulsion.  Figure  23  is  intro- 
duced to  show  the  effects  of  adding  a  little  acid  to  an  emul- 
sion of  oil  stabilized  in  an  alkali-protein  (alkali-casein). 
Since  neutral  casein  is  less  hydrophilic  than  the  alkali- 
protein,  the  emulsion  undergoes  ^' fatty  degeneration"  as 
soon  as  the  acid  is  added  to  it. 

3.  ANALOGY  BETWEEN  THE  CHEMICAL  CONDITIONS 
FAVORING  FATTY  DEGENERATION  AND  THOSE 
PRODUCING   COARSENING   IN   EMULSIONS. 

It  should  now  be  emphasized  that  there  exists  not  only 
entire  agreement  between  the  physical  phenomena  charac- 
terizing the  coarsening  of  an  emulsion  and  fatty  degenera- 
tion, but  also  between  the  chemical  conditions  governing  the 
two. 

Among  the  best  estabhshed  factors  now  recognized  as 
active  in  the  production  of  fatty  degeneration,  either  ex- 
perimentally or  under  clinical  circumstances,  are  poisoning 
with  phosphorus,  lead  or  arsenic,  anesthetizing  with  chlo- 
roform,^ ether  or  alcohol,  slow  poisoning  with  acid,  admin- 
istration of  phlorizin,  the  existence  of  diabetes,  anemia  ^  or 

^  See  in  this  connection  Evarts  A.  Graham:  Jour.  Exp.  Med.,  22,  48 
(1915). 

^  See  Thomas  R.  Boggs  and  Roger  S.  Morris:  Jour.  Exp.  Med.,  11,  553 
(1909). 


ON  FATTY  CHANGE  75 

general  or  local  circulatory  disturbances  (thrombosis  or 
embolism  with  infarction). 

When  it  is  recalled  that  hydrated  proteins  are  of  first 
importance  for  the  stabiHzation  of  fat  in  protoplasm,  it  at 
once  becomes  apparent  that  several  of  the  substances  above 
enumerated  are  of  a  type  to  favor  directly  the  dehydration 
of  certain  of  the  body  proteins.  Such  substances  may, 
therefore,  be  assimied  to  play  a  direct  part  in  the  initiation 
of  ''fatty  degeneration"  in  living  cells. 

But  phosphorus,  the  heavy  metals  and  the  anesthetics 
also  interfere  with  the  normal  oxidation  chemistry  of  the 
body  cells.  Such  interference,  as  known  since  the  classic 
studies  of  F.  Hoppe-Seyler,  T.  Araki,^  H.  Zillessen,^ 
etc.,  is  followed  by  an  abnormal  production  and  accumu- 
lation of  acids  in  the  poisoned  tissues.  The  effect  of  the 
acids  upon  protoplasm  has  been  discussed  many  times  be- 
fore. They  make  certain  of  the  cell  proteins  develop  an 
increased  capacity  for  holding  water.  When  water  is  avail- 
able, the  involved  cells  will,  in  consequence,  swell  (become 
edematous).^  As  the  cells  swell,  the  concentration  of  the 
protein  in  them  is  reduced,  wherefore  a  tendency  toward 
fatty  degeneration  develops  for  the  same  reason  that  a 
tendency  to  break  increases  in  an  emulsion,  as  the  hydro- 
philic  colloid  stabilizing  the  finely  divided  oil  is  diluted.* 

But  the  acids  which  thus  increase  the  hydration  capacity 
of  certain  cell  proteins  tend  at  the  same  time  to  decrease  that 
of  others.  For  instance,  certain  globulins,  which  in  the 
normal  cells  and  fluids  of  the  body  are  united  to  alkali  (as 
the  alkali-casein  of  milk),  possess  in  this  form  greater  hydro- 
phiHc  properties  than  when  neutral.^  The  addition  of  acid 
to  cells  containing  proteins  of  this  type  tends,  therefore,  to 

1  T.  Araki:  Zeitschr.  f.  Physiol.  Chem.,  16,  335  and  546  (1891);  Urid. 
19,  422  (1894). 

2  H.  Zillessen:  Zeitschr.  f.  Physiol.  Chem.,  15,  387  (1891). 

'  Martin  H.  Fischer:  (Edema  and  Nephritis,  2nd  edition.  New  York, 
1915. 

<  See  pages  37  and  47. 
«  See  page  33. 


76  FATS  AND  FATTY  DEGENERATION 

dehydrate  them.  The  swelUng  of  the  one  set  of  proteins 
combined  with  the  dehydration  of  a  second  yields  what 
the  pathologists  call  ^'cloudy  swelling/^  as  has  been  pre- 
viously pointed  out.^  Through  the  dehydration  of  this 
second  type  of  protein,  the  tendency  of  the  involved  cells 
to  approximate  pure  water  in  composition  is  further  in- 
creased, while  the  tendency  of  the  protoplasm  to  hold  apart 
the  fat  subdivided  in  it  is  correspondingly  diminished.  In 
other  words,  ^' fatty  degeneration"  is  aided  still  more. 

These  facts  will  serve  to  explain  what  the  pathologists 
have  so  often  noted,  namely,  that  ''cloudy  swelling''  is  both 
a  precursor  and  an  accompaniment  of  ''fatty  degeneration.'^ 

What  has  been  said  of  acid  intoxication  and  of  the  conse- 
quences incident  to  the  poisoning  of  man  or  animals  with 
the  metals,  with  phosphorus  or  the  anesthetics,  holds  also 
when  such  acid  intoxication  is  secondary  to  direct  carbo- 
hydrate starvation  or  the  indirect  starvation  consequent 
upon  phlorizin  or  pancreatic  diabeues.  It  holds,  too,  for 
the  abnormal  production  and  accumulation  of  acid  conse- 
quent upon  an  inadequate  oxygen  supply,  or  such  as  is 
incident  to  general  or  local  circulatory  disturbances  follow- 
ing heart  disease,  vascular  disease,  thrombosis  or  embolism. 

4.   TISSUE   RIGIDITY  AND   TISSUE    **  SOFTENING." 

We  should  Uke  next  to  call  attention  to  the  help  which 
the  colloid-chemical  study  of  emulsions  yields  toward  un- 
derstanding the  so-called  '^ softening'^  of  organs  suffering 
from  ^^ fatty  degeneration.'^  As  illustrated  particularly  well 
in  infarctions  of  the  kidney  or  brain,  or  in  the  after-effects 
of  nerve  section  (Waller's  degeneration),  the  involved 
areas  after  an  initial  swelling  with  graying  (cloudy  swell- 
ing) accompanied,  or  followed,  by  a  yellowing  (fatty  de- 
generation), tend  to  soften,  to  shrink  and  to  liquefy.     What 

1  See  Martin  H.  Fischer:  Kolloid-Zeitschrift,  8,  159  (1911);  also  (Edema 
and  Nephritis,  2nd  edition,  455,  New  York,  1915,  where  references  to  the 
older  literature  may  be  found. 


ON  FATTY  CHANGE 


77 


78 


FATS  AND  FATTY  DEGENERATION 


is  the  reason  for  this  softening  after  the  initial  increase  in 
firmness  due  to  the  sweUing? 


Fig.  25. 


§1. 

As  has  several  times  been  noted  by  different  authors, 
there  occurs  a  marked  increase  in  viscosity  whenever  an 
oil  is  emulsified  in  such  an  aqueous 
dispersion  medium  as  a  hydrated 
soap  or  a  hydrated  protein  solution. 
We  have  touched  upon  this  fact 
before.^  Figure  24  will  perhaps  illus- 
trate the  matter  better  than  many 
words.  In  the  two  flasks  are  con- 
tained, respectively,  120  cc.  of  cot- 
tonseed oil  and  20  cc.  of  a  7  percent 
potassium-soap  solution.  The  two 
are  labile  liquids.  But  let  the  oil  be 
emulsified  in  the  soap  and  the  result- 
ing mixture  becomes  so  stiff  that  the  mixing  vessel  con- 
taining it  may  be  turned  upside  down  without  its  flowing 
out.  The  same  great  viscosity  of  an  emulsion  is  shown  in 
Figure  25.  This  is  the 
picture  of  an  emulsion 
of  300  cc.  of  oil  in  25 
cc.  of  25  percent  potas- 
sium-soap. 

Let  us  next  observe 
what  happens  when 
this  stiff  oil-in-soap 
emulsion  is  broken  by 
any  means  whatso- 
ever, as  through  simple 
drying,  the  addition  of 

a  little   acid   or   alcohol,    or   admixture  with  a  properly 
chosen  salt.    As  the  emulsion  breaks,  there  is  a  fall  in  vis- 


FiG.  26. 


*  See  page  40. 


ON  FATTY  CHANGE  79 

cosity  back  to  that  of  the  individual  constituents  of  the 
emulsion.  While  a  metal  rod  is  held  in  any  given  position 
in  the  viscid  emulsion  of  Figure  25,  it  falls  to  the  edge  of 
the  container  as  soon  as  the  emulsion  is  broken,  as  shown 
in  Figure  26. 

MiLch  of  the  normal  viscosity  or  rigidity  of  the  tissues  is  due 
to  their  emulsion  character.  The  '^ softening'^  of  the  organs  as 
observed  in  various  pathological  states  is  dv^  to  a  breaking  of 
this  emulsion, 

§2. 

Some  corollaries  of  this  simple  conclusion  are  of  biological 
interest.  It  should  first  be  emphasized  that  emulsions  are, 
by  definition,  diphasic  or  polyphasic  systems  of  mutually 
immiscible  liquids.  Oil-in-hydrated  protein,  oil-in-hydrated 
soap,  etc.,  are,  therefore,  not  the  only  emulsions  to  be 
thought  of  in  the  case  of  protoplasm.  We  may  have  also 
emulsions  of  one  kind  of  hydrated  protein  in  a  second^  or 
of  hydrated  carbohydrates  in  hydrated  protein,  etc.  So  even 
in  the  absence  of  fat  (which  substance  is  to  be  thought 
of  particularly  in  such  fat -rich  organs  as  the  peripheral 
nerves  and  the  central  nervous  system)  we  may  obtain 
highly  viscid  complexes  from  emulsification  in  each  other 
of  what  are,  to  begin  with,  mobile  Uquids.^  We  find  in 
these  considerations  an  explanation  of  those  properties  of 
protoplasm  which  have  inclined  us  to  think  of  it,  on  the  one 
hand,  as  ^^solid,^'  on  the  other,  as  '^ liquid,''^  Elasticity  and 
maintenance  of  form  argue  for  the  soHd  natiu-e  of  proto- 
plasm; that  it  shows  surface  tension  phenomena,  that  it 
allows  materials  to  diffuse  into  and  through  it,  and  that  it 
acts  chemically  as  though  it  were  liquid,  argue  for  its  fluid 
character.  The  emulsion  character  of  protoplasm  explains 
why  the  two  may  be  associated  as  they  are.  Being  com- 
posed for  the  most  part  of  phases  which  are  by  themselves 
liquid,  there  exists  no  a  priori  reason  why  the  essential 

^  These  systems  are  now  being  studied  in  our  laboratory  and  will  be  re- 
ported upon  later. 


80 


FATS  AND  FATTY  DEGENERATION 


properties  of  the  liquids  should  be  lost  when  they  are  mixed 
into  each  other.  But,  if  the  liquids  are  mutually  insoluble 
(practically),  emulsions  are  formed;  and  as  this  happens,  the 

viscosity  of  the  mixture 
rises  until  the  properties 
of  solids  are  approximated. 

§3. 

It  behooves  us,  in  con- 
nection with  certain  find- 
ings characteristic  of  tissue 
softening  (as  observed  in 
the  brain,  for  example), 
to  study  a  little  more 
closely  the  changes  observ- 
able in  a  breaking  or  a 
broken  oil  emulsion.  In 
Figure  27  is  shown  an  oil- 
in-soap  emulsion  which 
has  been  broken  through 
mere  dilution  with  water 
(which  not  only  dilutes 
the  soap  to  below  the  con- 
centration necessary  for 
the  maintenance  of  the 
emulsion  but  destroys  its 
hydrophilic  characteris- 
tics, since  the  soap  goes 
into  "true"  solution  in 
much  water).  At  the  top 
of  the  liquid  column  is 
seen  a  layer  of  pure  oil  (a). 
The  white  collar  below  this  (6)  is  an  emulsion  of  soap-water 
in  oil.  Next  (c)  comes  an  emulsion  of  oil  in  soap-water, 
and  lowest  in  the  bottle  is  (practically)  pure  soap-water  (d). 
When  studied  microscopically  the  pure  oil  shows  nothing; 


Fig.  27. 


ON  FATTY  CHANGE  81 

the  dark  spots  in  Figure  28  are  dust  particles  that  in- 
dicate that  the  oil  layer  is  really  in  focus.  In  Figure  29 
is  shown  the  appearance  of  the  white  collar;  the  globules 
are  soap-water  emulsified  in  the  oil.  Figure  30  is  prac- 
tically indistinguishable  from  Figure  29,  but  it  represents 
the  opposite  type  of  emulsion,  namely,  one  of  oil  in  soap- 
water.  Figure  31  is  taken  from  the  bottom  of  the  tube. 
A  few  scattered  globules  of  (coUoidally)  divided  oil  in  the 
process  of  Brownian  movement  may  be  seen;  the  field  is, 
in  other  words,  practically  pure  soap-water. 

Pathological  examination  of  the  material  from  a  well- 
softened  area  (as  from  the  brain)  shows  this  to  consist  of 
the  same  types  of  materials.  There  are  found  large  glob- 
ules of  clear  oil,  oil  with  water  emulsified  in  it,  water  with 
oil  emulsified  in  it,  and  water.  The  four  materials  are  not, 
of  course,  as  pure  as  here  indicated.  Dissolved  and  pre- 
cipitated protein,  for  example,  is  Ukely  to  contaminate  any 
of  the  phases,  just  as  the  particles  of  dissolved  or  precipi- 
tated protein  or  soap  contaminate  the  different  divisions 
of  an  emulsion  prepared  and  broken  under  laboratory  con- 
ditions. 

6.   FURTHER  HISTORICAL  REMARKS. 

With  our  concept  in  mind  that  fatty  degeneration  repre- 
sents merely  a  coarsening  of  the  normal  fat-in-protoplasm 
emulsion,  under  circumstances  and  through  agencies  which 
lead  to  the  dilution  and  dehydration  of  the  hydrophilic 
colloids  which  normally  keep  the  fat  apart  in  finely  divided 
form,  we  need  now  to  take  a  look  backward  at  the  wealth 
of  experimental  and  literary  material  available  on  the  sub- 
ject of  fatty  degeneration,  in  order  to  emphasize  the  value 
of  certain  older  researches. 

Of  first  interest  in  this  direction  are  the  studies  of  Hau- 
SER,^  and  F.  Kraus  ^  who  found  that  organs  removed  from 
the  body  and  kept  under  sterile  conditions  gradually  un- 

1  Hauser:  Arch.  f.  exp.  Path.  u.  Pharm.,  20,  162  (1885). 

2  F.  Kraus:  Arch.  f.  exp.  Path.  u.  Pharm.,  22,  174  (1887). 


82 


FATS  AND  FATTY  DEGENERATION 


Fig.  28. 


Fig.  29. 


ON  FATTY  CHANGE 


83 


Fig.  60. 


Fig.  31. 


84         FATS  AND  FATTY  DEGENERATION 

dergo  a  ^^ fatty  degeneration.'^  Similar  observations  have 
been  made  since  by  F.  Siegert/  A.  Orgler,^  Waldvogel  ^ 
and  others.  Several  of  these  authors  have  used  this  post 
mortem  appearance  of  fatty  degeneration  as  an  effective 
argument  against  the  view  that  fatty  degeneration  either 
needs  to  be,  or  is,  preceded  by  a  "fatty  infiltration"  of  the 
involved  tissues.  In  all  of  these  experiments  there  is,  of 
course,  no  possibility  of  getting  an  increased  infiltration  of 
fat,  and  in  many  of  them  even  the  possibilities  of  an  in- 
creased fat  production  post  mortem  from  some  constituent 
of  the  cell  protoplasm  are  not  at  hand. 

We  should  ourselves  interpret  these  findings  by  saying 
that  the  normal  fat  content  of  these  organs  simply  becomes 
more  easily  visible  with  the  changes  consequent  upon  their 
removal  from  the  body.  We  do  not  even  think  it  neces- 
sary to  call  upon  complicated  enzymatic  processes  to  explain 
why  the  fatty  change  must  occur  post  mortem.  As  soon 
as  organs  of  warm-blooded  animals  are  deprived  of  their 
circulation,  they  begin  to  develop  lactic  and  other  acids 
which  in  these  "dead"  organs  act  in  the  manner  described 
above  when  discussing  the  fatty  degeneration  of  living  tis- 
sues. The  acids  bring  about  a  dilution  and  a  dehydration 
of  various  body  colloids  and  so  the  finely  divided  fat,  origi- 
nally held  apart,  runs  together  into  larger  globules. 

In  connection  with  the  question  of  the  chemical  condi- 
tions which  thus  make  it  possible  for  the  fat  found  normally 
in  the  cells  to  flow  together  into  larger  droplets,  the  observa- 
tions of  V.  RuBOW^  are  of  much  interest.  Rubow  holds 
that  normally  fat  is  dissolved  in  the  body  fluids  and  cell 
protoplasm  and  hence  is  invisible.  This  "dissolved"  state 
of  the  fat  is  maintained  through  the  presence  of  alkali  in 
these  fluids  and  cells.  If  the  amount  of  alkali  is  diminished, 
either  through  an  increased  production  or  a  decreased  re- 

1  F.  Siegert:  Hofmeister's  Beitrage,  1,  114  (1901). 

2  A.  Orgler:  Virchow's  Arch.,  176,  413  (1904). 

3  Waldvogel:  Zentralbl.  f.  Stoffwecbsel  u.  Verdauungskr,  4,  405  (1903); 
Virchow's  Arch.,  177,  1  (1904);  Zeitschr.  f.  physiol.  Chem.,  42,  200  (1904). 

4  V.  Rubow:  Arch.  f.  exp.  Path.  u.  Pharm.,  62,  173  (1905). 


ON   FATTY   CHANGE  85 

moval  of  acids  from  the  tissues,  Rubow  thinks  that  the 
solubiUty  of  the  fat  is  thereby  decreased,  wherefore  it 
separates  out  in  coarse  form.  The  views  of  Rubow  have 
found  httle  acceptance  because  to  keep  the  fat  '' dissolved, '^ 
enough  alkah  must  be  present  to  convert  the  fat  into  soap, 
and  chemical  analysis  shows  that  the  tissues  richest  in  fat 
contain  no  amount  of  alkali  adequate  for  such  purpose. 
The  fat  of  the  cells  is,  moreover,  neutral  fat  and  not  soap. 
But  in  pointing  out  that  many  of  the  best  known  methods 
of  producing  fatty  degeneration  are  such  as  lead  to  an  in- 
creased production  or  accumulation  of  acids  in  the  involved 
cells,  and  in  emphasizing  this  as  an  important  factor  in 
the  production  of  fatty  degeneration,  he  has  made  a  funda- 
mental contribution  to  the  subject.  The  acids  do  not  make 
a  previously  soluble  fat  insoluble,  but,  as  indicated  above, 
these,  and  similar  agencies,  through  the  destruction  of  hy- 
drophilic  colloids,  favor  the  coalescence  of  finely  divided 
and  therefore  invisible  droplets  of  fat  into  larger,  more 
readily  visible  droplets. 

The  view  that  in  ''fatty  degeneration"  the  fat  which  be- 
comes visible  in  the  cell  is  derived  from  a  precursor  of  some 
sort,  like  lecithin,  we  need  not  discuss.  Carefully  made 
quantitative  chemical  analyses  now  show,  on  the  one  hand, 
that  even  in  the  most  extreme  cases  of  ''fatty  degenera- 
tion" no  decrease  may  be  observable  in  the  lecithin  con- 
tent normal  for  the  involved  cell,  while,  on  the  other  hand, 
amounts  of  fat  are  found  in  certain  cells  that  have  under- 
gone "fatty  degeneration"  which  exceed  enormously  any 
that  could  have  been  produced  from  the  amounts  of  lecithin 
found  in  the  cell. 


VI.   THE  ADIPOSE  TISSUES  AND  THE    FATTY 
SECRETIONS. 


VI.  THE  ADIPOSE  TISSUES  AND  THE  FATTY 
SECRETIONS. 

Thus  far  we  have  discussed  the  problem  of  fat  m  cells  and 
secretions  only  under  circumstances  in  which  the  amount 
of  the  fat  has  remained  relatively  low.  Even  figures  alleged 
to  be  anormally  high  (such,  for  example,  as  are  encountered 
in  tissues  with  fatty  degeneration  or  fatty  infiltration)  do 
not  run  above  some  forty  percent  of  the  moist  weight  of 
the  organ.  Perls  ^  observed  this  value  in  fatty  infiltra- 
tion of  the  liver  of  a  chronic  alcohohc. 

To  get  fat  values  in  cells  or  secretions  which  exceed 
forty  percent,  we  need  again  to  pass  into  the  physiological 
realm. 

1.   THE  FATTY  TISSUES. 

According  to  Gorup-Besanez,^  human  bone  marrow  con- 
tains 96.0  percent  of  fat,  and  adipose  tissue  contains  82.7 
percent.  Table  V  gives  another  analysis  of  human  adipose 
tissue,  as  well  as  several  of  fats  from  animal  sources. 


TABLE  V. 
Composition  of  Various  Adipose  Tissues. 

Fat. 

Water. 

Protein. 

Human  fat ' 

82.5 
81.9 
64.0 

77.7 

15.0 
7.9 

18.8 
13.7 

2  5 

Pig  fat  2 

1  8 

Bacon^ 

9  6 

Suet  3 

4  6 

»  Volkmann:   Vierordt's  Daten  und  Tabellen,  190,  Jena,  1888. 

2  Atwater  and  Bryant:  Quoted  by  Graham  Lusk,  Science  of  Nutrition,  2nd  edition,  366, 
Philadelphia,  1909. 

»  Atwater  and  Bryant:   I.  c.  366. 

The  features  of  interest  in  connection  with  this  table 

1  Perls:    Cited  by  J.  George  Adami,  Principles  of  Pathology,  1,  821, 
Philadelphia,  1908. 

2  Gorup-Besanez:    Quoted  by  W.   D.   Halliburton,    Schafer's  Text- 
Book  of  Physiology,  1,  17,  Edinburgh,  1898. 

89 


90         FATS  AND  FATTY  DEGENERATION 

are  not  only  the  high  percentages  of  fat  but  the  high  per- 
centages of  water  found  in  the  tissues  named.  Let  it  be 
noted  that  some  seven  to  fifteen  percent  of  water  is  con- 
stantly encountered  in  all  such  tissues.  Why  are  these 
amounts  so  constant,  and  how  is  the  water  carried  in  the 
fat  tissues?  As  readily  apparent,  the  figures  he  in  all  cases 
beyond  the  simple  ''solubility"  limits  of  water  in  fat. 

The  adipose  tissues,  too,  are  emulsions,  but  of  the  type  of 
water-in-fat  (hydrated  colloid-in-fat).  The  proofs  for  this 
contention  are  several.  First,  the  high  proportion  of  the 
fat  in  the  total  bulk  constituting  the  fatty  tissues  takes  the 
mixture  to  or  beyond  the  ''breaking"  point  of  the  oil-in- 
hydrated  colloid  type  of  emulsion.  Second,  the  fatty  tis- 
sues impart  a  greasy  ' '  feel ' '  when  rubbed  between  the  fingers, 
and  "oil"  a  paper  placed  in  contact  with  them.  But  the 
best  proof  is  perhaps  furnished  by  direct  microscopic  ex- 
amination of  thin  shavings  or  crush  preparations  of  the  fatty 
tissues  themselves.  When  tiny  fragments  of  adipose  tissue 
are  removed  from  the  central  portions  of  the  fat  depots  of 
different  animals  and  examined  microscopically,  pictures 
like  those  shown  in  Figures  32,  33  and  34  are  obtained. 
Figure  32  is  fresh  pig's  fat.  The  hydrated  colloid-in-oil 
type  of  emulsion  is  not  destroyed  even  through  subjection 
to  the  processes  of  salting  and  smoking  by  which  such  fresh 
pig's  fat  is  converted  into  the  bacon  shown  in  Figure  33. 
Figure  34  presents  the  appearance  of  fresh  rabbit's  fat. 

It  will  be  noted  that  the  fats  found  in  all  these  adipose 
tissues  have  rather  low  melting  points.  In  adipose  tissues 
containing  high  melting  point  fats  (like  beef  suet)  the  drop- 
let character  of  the  aqueous  phase  in  the  fat  is  less  apparent. 
This  is  because  the  water  is  crushed  out  of  shape  between 
the  palmitin,  stearin  and  other  high  melting  point  fats 
which  constitute  the  bulk  of  these  tissues.  Actual  crystal- 
lization of  the  bulk  of  these  fats  is  readily  observable, 
especially  in  the  cold.  When  the  tissues  are  kept  at  body 
temperature,  or  above,  the  liquid  droplets  making  up  the 
aqueous  phase  become  readily  visible. 


THE  ADIPOSE  TISSUES  AND  THE  FATTY  SECRETIONS     91 

What  has  been  said  of  the  adipose  tissues  of  animals 
holds  also  for  the  sohd  tissues  of  plants  which  are  high  in 
fat.  An  illustrative  series  of  analyses  showing  the  compo- 
sition of  nuts  is  given  in  Table  VI. ^  Composition,  micro- 
scopic analysis,  and  reaction  to  feel  and  paper  again  prove 
that  whenever  the  proportion  of  fat  runs  high,  the  nut  consists 
essentially  of  an  emulsion  of  water  {hydrated  colloid)  in  fat. 
Of  the  nuts  listed  in  Table  VI,  those  standing  highest  in  the 
list  are  those  which  in  their  natural  state  are  most  likely  to 
be  greasy,  while  those  lowest  in  the  hst  are  more  commonly 
mealy.  In  any  nut,  mere  drying  incident  to  ageing  in- 
creases its  greasiness,  while  this  change  is  often  hastened 
for  culinary  reasons  by  oven  drying  or  roasting  the  nuts. 


TABLE  VI. 
Composition  of  Nuts. 


Nut. 


Hickory.  . 
Filbert .  .  . 
Butternut 
Almond . . 
Cocoanut 
Peanut  . . 
Chestnut. 


Fat. 

Water. 

Protein. 

Carbohy- 
drate. 

60.7 

3.7 

13.1 

10.3 

58  8 

3.7 

13.3 

11.7 

55  1 

4.4 

23.7 

3.2 

49.4 

4.8 

17.8 

15.6 

45.5 

14.1 

4.8 

25  1 

34.7 

9.2 

21.9 

22  0 

4.9 

45  0 

5  3 

37.9 

Ash. 


1.6 
1.8 
2  2 
1.5 
1.3 
1.5 
1.0 


2.   THE   FATTY   SECRETIONS. 


Just  as  the  adipose  tissues  are  seen  to  be  emulsions  of 
hydrated  colloid-in-fat,  so  are  the  fatty  secretions.  How 
the  fatty  secretions  come  to  be  formed  from  animal  or 
vegetable  protoplasm  (which,  except  in  the  case  of  the 
essentially  adipose  tissues,  represents  an  emulsion  of  fat-in- 
hydrated  colloid)  is  well  illustrated  in  the  phenomena  ac- 
companying the  change  of  milk  into  butter. 

Whole  milk  represents,  as  universally  known,  an  emul- 
sion of  oil  in  a  diluted  set  of  hydrophilic  colloids.     During 

1  Atwater  and  Bryant:  Quoted  by  Graham  Lusk,  Science  of  Nutri- 
tion, 2nd  ed.,  374,  Philadelphia,  1909. 


92 


FATS  AND  FATTY  DEGENERATION 


i-iG.  62. 


■ 

f .  ~ .  '^i^B 

■ 

■ 

^^^ 

^^^^Hb 

tM^               '  i 

H^^^l 

^^H 

^^^^^^^^^^^^^^^  •it!^ 

H     ' 

^ 

P 

^B 

■ 

■ 

' 

HK 

'■*!                      '"" 

Fig.  33. 


THE  ADIPOSE  TISSUES  AND  THE  FATTY  SECRETIONS     93 


the  lactation  period,  the  secretory  cells  of  the  mammary 
glands  grow  rapidly,  they  become  highly  charged  with  fat, 
the  fat  coalesces  into  readily  visible  particles  (fatty  degen- 
eration) and  finally  the  gradually  swelling  cells  bm-st  to 
yield  the  fat-in-hydrated  colloid  emulsion  which  is  called 
milk.  Whole,  unchanged  milk  shows  little  tendency  to 
form  butter.     The  tendency  to  do  so  is  increased,  first,  by 


Fig.  34. 

allowing  the  fat  particles  in  the  unit  volimae  of  hydrated 
colloid  to  concentrate  (through  letting  the  cream  rise  or  by 
mechanical  separation  of  the  cream) ,  and  second,  by  aiding 
the  dehydration  of  the  colloids  to  which  the  water  is  so 
largely  bound,  as  by  allowing  the  cream  to  sour.  Since 
the  hydrated  colloids  tend  to  collect  in  the  surface  layers 
between  the  fat  particles  and  the  aqueous  phase  of  the 
cream,  efforts  are  made  to  break  these  layers,  and  so  to 
hasten  coalescence  of  the  fat  droplets,  by  churning.  The 
combined  efforts  therefore  bring  about  a  progressive  increase  in 
the  concentration  of  the  oil  with  a  decrease  in  the  concentration 


94 


FATS  AND  FATTY  DEGENERATION 


0/  the  hydrated  colloid  until  the  instability  of  the  oil-in-hydrated 
colloid  emulsion  becomes  so  great  as  to  ^'break^'  and  yield  the 
hydrated  colloid-in-fat  emulsion  which  we  call  butter. 

This  concept  may  be  tested  in  various  ways.  Milk  and 
cream  '^wet'^  paper,  are  not  greasy  to  the  touch  and  micro- 
scopically show  particles  of  oil  divided  in  a  continuous 
aqueous  phase. 


Fig.  35. 

Butter,  on  the  other  hand,  ^^oils"  paper,  feels  greasy, 
and  microscopically  is  seen  to  consist  of  an  emulsion  in 
which  the  aqueous  phase  (hydrated  colloid)  is  finely  divided 
in  droplet  form  in  the  continuous  oil  phase. 

Table  VII  ^  illustrates  the  changes  in  chemical  composi- 
tion which  milk  shows  in  its  progress  toward  butter.  To 
the  table  has  been  added  an  analysis  of  oleomargarin  which 
not  only  chemically  stands  close  to  true  butter,  but  which, 
as  shown  in  Figure  35,  is  quite  like  it  in  its  physical  aspects 

1  Atwater  and  Bryant:  Quoted  by  Graham  Lusk,  Science  of  Nutrition, 
2nd  ed.,  370,  Philadelphia,  1909. 


THE  ADIPOSE  TISSUES  AND  THE  FATTY  SECRETIONS     95 

also.     It  is,  in  fact,  really  an  emulsion  of  hydrated  colloid- 
in-fat. 

TABLE  VII. 
Composition  of  Dairy  Products  and  Oleomargarin. 


Fat. 

Water. 

Protein. 

Whole  milk 

3.8 
17.6 
80.8 
78.9 

87 

74 
11 
9.5 

3.2 

Cream 

Butter 

2.4 
1.0 

Oleomargarin 

1.2 

The  formation  of  the  fatty  secretions  by  animals  or  plants 
represents  a  change  from  an  oil-in-aqueous  phase  type  of 
emulsion  to  an  aqueous  phase-in-oil  type,  which  is  entirely 
analogous  to  the  change  of  milk  into  butter.  Under  natural 
conditions,  this  change  is  produced  by  drying  alone. 

In  illustration  of  what  happens  in  the  formation  of  the 
fatty  secretions,  we  may  study  the  behavior  of  ear  wax. 
Its  chemical  composition  is  indicated  in  Table  VIII,  taken 
from  Petrequin  and  Chevalier.^ 


TABLE  VIII. 
Percentage  Composition  of  Ear  Wax. 


Fat. 

Water. 

Potassium 
Soap. 

Other 

Organic 

Materials. 

Ash. 

From  adults 

26 
30.5 

10 

11.5 

52 
41 

12 
17 

Traces 

From  the  aged 

The  most  striking  features  in  these  analyses  are  the  char- 
acteristic, rather  high,  water  percentages,  the  enormous 
(colloid)  soap  values  and  the  rather  high  fat  contents.  In 
other  words,  ear  wax  is  a  mixture  of  hydrated  soap  and  fat. 
Coming  as  it  does  from  a  set  of  sebaceous  glands,  the  pro- 
toplasm of  which,  to  begin  with,  represents  an  emulsion  of 
oil-in-hydrated  colloid,  the  greasy  feel  of  ear  .w^ax  and  its 

^  Petrequin  and  Chevalier:   Quoted  by  F.  Hopp 
gische  Chemie,  704,  Berlin,  1881. 


EYLER,  Physiolo- 


96         FATS  AND  FATTY  DEGENERATION 

oily  properties  already  indicate  that  in  the  process  of  secre- 
tion and  in  the  process  of  drying  after  secretion,  a  change 
must  have  occurred  to  the  hydrated  colloid-in-oil  type  of 
emulsion.  Microscopic  examination  bears  this  out.  In 
Figure  36  is  shown  some  moist  ear  wax.  The  droplets  of 
hydrated  colloid  are  readily  apparent.  As  the  ear  wax 
dries  more  perfectly,  the  soap  which  constitutes  the  bulk  of 
the  hydrated  colloid  in  the  oil  tends  to  become  more  flaky 
or  crystalline.  The  droplets,  therefore,  largely  vanish  and 
the  appearance  shown  in  Figure  37  ensues.  This  is  micro- 
scopically similar  to  that  shown  by  any  hydrated  soap-oil 
mixture  in  which,  through  evaporation,  an  emulsion  of  the 
type  of  aqueous  phase-in-oil  has  become  established.  Fig- 
ure 38  is  a  photo-micrograph  of  such  a  hydrated  soap-in-oil 
emulsion  produced  through  gradual  evaporation  of  the  water 
from  what  was  originally  an  oil-in-hydrated  soap  emulsion. 
The  clear  streak  in  the  middle  of  the  field  is  pure  oil;  on 
each  side  of  it  is  seen  a  hydrated  soap-in-oil  emulsion. 

In  order  not  to  lengthen  our  discussion  unduly,  let  it 
simply  be  noted  that  what  was  said  here  regarding  ear  wax 
holds  also  for  sebum,  smegma  and  vernix  caseosa.  It  holds 
also  for  the  fatty  secretions  encountered  pathologically  in 
cysts,  tumors,  etc.,  and  similarly  for  the  oily,  fatty  and 
resinous  secretions  given  off  by  different  plants. 

3.   OPTICAL   CHANGES   INCIDENT  TO   PHYSICAL 
CHANGES   IN   EMULSIONS. 

Much  interest  is  attached  to  the  gross  changes  which 
accompany  the  transformation  of  an  oil-in-hydrated  colloid 
emulsion  into  one  of  a  hydrated  colloid-in-oil  type.  As 
already  emphasized,  simple  drying  leads  to  this  transforma- 
tion in  many  oil-in-hydrated  colloid  mixtures.  An  illus- 
trative example  is  offered  in  the  drying  of  an  oil-in-hydrated 
soap  emulsion.  When  a  stiff  emulsion  of  this  type  is  smeared 
as  a  rather  thick  layer  over  the  surface  of  a  cylinder,  as 
shown  in  Figure  39  the  water  gradually  evaporates.     Dur- 


THE  ADIPOSE  TISSUES  AND  THE  FATTY  SECRETIONS     97 


Fig.  36. 


Fig.  37. 


98 


FATS  AND  FATTY   DEGENERATION 


ing  this  evaporation  it  is  first  to  be  observed  that  the  mix- 
ture, which  originally  was  intensely  white,  becomes  trans- 
lucent and  finally  so  transparent  that  printing  may  be 
read  through  it.  If  the  drying  is  continued  beyond  this 
point,  beads  of  oil  appear  upon  the  surface  of  the  emulsion, 
which  gradually  increase  in  size,  coalesce  and  drip  to  the 


Fig.  38. 

bottom.  The  horizontal  layer  in  the  bottom  of  the  cyUnder 
in  Figure  39  is  pure  oil  that  has  collected  in  this  way. 

The  formation  of  such  oil  beads  occurs  also  in  drying 
oil-in-hydrated  protein  emulsions.  An  illustration  of  this 
process  is  seen  in  Figure  40  which  is  a  slightly  enlarged 
photograph  of  a  gradually  drying  mass  of  egg  yolk. 

The  gradual  change  from  opaque  whiteness  to  translu- 
cency  and  final  transparency  with  drying  of  the  emulsion 
is  illustrated  further  in  Figiu-e  41.     Over  a  in  the  picture  is 


THE  ADIPOSE  TISSUES  AND  THE  FATTY  SECRETIONS     99 


shown  a  glass  plate  freshly 
smeared  with  an  oil-in-hydrated 
colloid  (soap  or  protein)  emul- 
sion. The  design  placed  behind 
this  plate  cannot  be  seen.  Over 
b  in  the  photograph  is  shown  a 
similar  smear  made  some  hours 
earlier  and  from  which  the  water 
has  been  allowed  to  evaporate; 
this  plate  has  become  so  trans- 
parent that  the  design  is  readily 
visible  through  it. 

This  gradual  increase  in  trans- 
parency may  also  be  observed 
microscopically  as  shown  in  the 
case  of  a  coarse  oil-in-soap 
emulsion  in  Figure  42.  The 
field  marked  b  is  from  the  drying 
edge  of  the  microscopic  speci- 
men; the  light  passes  through 
this  portion  of  the  field  with  less 
refraction  than  through  the  remaining  portion  a  included 
in  the  photomicrograph. 


Fig.  40. 


100 


FATS  AND  FATTY  DEGENERATION 


The  behavior  of  drying  oil-in-hydrated  colloid  emulsions 
is  analogous  to  various  biological  processes.     The  experi- 


FlG.  42. 


ments  on  emulsions  show  how  such  dehydration  effects  as 
are  incident  to  simple  drying  lead  up  to  and  permit  the 
separation  of  the  fat  phase  in  almost  pure  form  —  a  process 
analogous  to  the  secretion  of  almost  pure  fat  by  various 


THE  ADIPOSE  TISSUES  AND  THE  FATTY   SECRETIONS      101 

animal  or  plant  cells.  Second,  the  clearing  of  such  diphasic 
systems  explains  how  tissues,  originally  opaque,  may  be- 
come entirely  transparent.  Tissues  composed  of  oil-in- 
hydrated  protein,  or  of  hydrated  protein  in  a  second  hy- 
drated  protein,  for  example,  and  originally  opaque,  may 
through  simple  changes  in  the  water  content  of  the  one 
phase  permit  the  indices  of  refraction  of  the  two  phases  to 
come  so  close  together  that  they  become  entirely  trans- 
parent. It  is  to  considerations  of  this  kind  that  we  must 
turn,  we  think,  when  we  attempt  to  understand  how  the 
formation  is  made  possible  of  such  clear  tissues  as  com- 
pose the  cornea,  Wharton's  jelly  of  the  umbilical  cord,  the 
hyalin  structures  constituting  cartilage,  etc.,  from  the  opaque 
structures  which  were  their  antecedents. 


VII.   ON  THE  NATURAL  AND  ARTIFICIAL 
PRODUCTION  OF  MILK. 


VII.  ON  THE  NATURAL  AND  ARTIFICIAL 
PRODUCTION  OF  MILK. 

1.  INTRODUCTION. 

From  what  has  been  said  in  the  previous  sections,  it  is 
apparent  that  the  ordinary  cell  is  an  emulsion  of  a  fraction 
to  several  percent  of  fat  and  lipoids  in  a  hydrated  colloid. 
We  followed  in  the  last  section  the  consequences  of  increas- 
ing the  percentage  of  the  fat  in  such  a  system.  When, 
either  through  an  increased  laying  down  of  fat  in  a  cell  or 
through  simple  loss  of  the  water  from  a  cell,  we  increase  the 
concentration  of  the  fat  to  beyond  a  certain  critical  point, 
a  transformation  of  the  original  oil-in-water  type  of  emul- 
sion to  one  of  the  water-in-oil  type  takes  place;  in  other 
words,  either  adipose  tissue  or  a  fatty  secretion  is  formed, 
depending  upon  whether  the  oil  concentration  or  water  loss 
occurs  within  the  tissues  themselves  or  upon  the  surface  of 
an  animal  or  plant. 

Let  us  now  look  at  the  results  of  the  opposite  type  of 
change.  What  happens  if,  instead  of  decreasing  the  amount 
of  water  in  the  ordinary  fat-in-hydrated  colloid  which  consti- 
tutes our  cells,  we  increase  it?  Under  these  circumstances 
'^milk'^  is  produced. 

2.  THE  NORMAL   (BIOLOGICAL)   PRODUCTION  OF 

MILK. 

This  is,  first  of  all,  the  method  which  nature  uses  in  the 
production  of  milk.  As  histological  study  shows,  the  alve- 
oli of  an  active  mammary  gland  consist  originally  of  a  single 
layer  of  nearly  cubical  gland  cells.  In  the  process  toward 
milk  production,  these  cells  increase  in  length,  pushing  out 
toward  the  lumen  of  the  alveolus.  The  portions  farthest 
from  the  basement  membrane  to  which  these  cells  are  at- 
tached (farthest,  we  would  prefer  to  say,  from  the  capil- 

105 


106  FATS  AND  FATTY  DEGENERATION 

laries  which  supply  oxygen  to  the  gland  cells)  begin  to  show 
the  appearance  of  fatty  droplets  in  them.  When  morpho- 
logical pathologists  describe  the  process,  they  say  that  the 
peripheral  portions  of  the  secreting  cell  undergo  ''fatty 
degeneration."  The  facts  are  that  the  distal  portion  is 
swollen,  often  granular  (''cloudy  swelling")  and  studded 
with  fatty  granules.  These  peripheral  portions  of  the  cell 
finally  swell  so  much  that  they  "go  into  solution"  and 
thus  form  "milk."  The  portion  of  the  cell  which  remains 
and  is  attached  to  the  basement  membrane  is  then  again 
cubical  and  again  begins  the  series  of  changes  just  described. 
Expressed  in  the  terms  of  emulsion  chemistry,  this  set  of 
cellular  changes  represents  the  original  emulsion  of  fat  in 
the  concentrated  hydrophilic  colloid  (corresponding  to  the 
original  cubical  cell)  becoming  richer  in  water.  One  of 
the  colloids  in  the  cell  swells  while  a  second  is  precipitated. 
Together,  this  yields  the  "cloudy  swelling"  which,  however, 
in  the  terms  of  emulsion  chemistry  means  not  only  a  de- 
crease in  the  concentration  of  the  hydrophilic  colloids  of 
an  emulsion  but  a  decreased  capacity  for  holding  water  on 
the  part  of  some  of  them.  The  tiny  fat  droplets  of  the 
original  emulsion  therefore  tend  to  run  together,  to  form 
larger  ones  which  begin  to  appear  in  the  distal  portions  of 
the  cell  (fatty  degeneration).  When  this  coarsened  emul- 
sion is  still  further  diluted,  when,  in  other  words,  the  cells 
swell  to  the  "solution"  point,  there  results  an  emulsion  of 
fat  droplets  in  a  dilute  mixture  of  proteins  (albumins  and 
globulins)  to  which  we  are  in  the  habit  of  attaching  the 
name  "milk."  What  happens  is  illustrated  in  Figure  43. 
When  such  a  concentrated  emulsion  of  oil-in-soap  as  is 
shown  in  the  first  jar  in  Figure  6  or  of  oil-in-protein  as  is 
shown  in  Figure  7  is  merely  diluted,  the  "milks"  shown 
in  Figure  43  result.  These  milks  are  readily  miscible  with 
all  amounts  of  water,  have  the  texture  of  the  natural  milks, 
readily  wash  out  of  their  containers,  do  not  feel  greasy  and, 
on  standing,  give  rise  to  such  a  cream  layer  as  is  shown  in 
Figure  44. 


NATURAL  AND  ARTIFICIAL  PRODUCTION  OF  MILK       107 


108  FATS  AND   FATTY  DEGENERATION 


3.   THE   ARTIFICIAL   PRODUCTION   OF   MILK. 

As  a  matter  of  fact,  we  can  not  only  mimic  nature  and 
test  out  the  correctness  of  these  deductions  by  repeating 
the  whole  series  of  changes  under  laboratory  conditions, 
but  in  so  doing  discover  laboratory  methods  of  making 
milk  artificially  and  of  a  type  and  composition  which  imi- 
tates perfectly,  not  only  cow's  milk  but  any  milk  for  which 
we  may  have  the  necessary  chemical  constituents.  Or  we 
may  thus  ''synthesize"  milks  which  within  wide  limits  may 
have  any  composition  we  may  choose  to  give  them. 

A  ''synthesis"  of  milk  has,  independently  of  us,  been 
accomplished  by  A.  W.  Bos  worth.  ^  Bosworth  approached 
the  problem  from  a  chemical  point  of  view.  After  first 
obtaining  in  pure  form  the  characteristic  fats,  salts,  carbo- 
hydrates and  proteins  of  milk,  he  mixed  them  together 
again  with  the  necessary  water  to  yield  the  artificial  milk 
he  desired.  Then,  by  working  at  temperatures  which 
would  make  the  fat  fluid  and  by  running  the  whole  through 
a  homogenizer,  he  produced  the  emulsion  necessary  to  imi- 
tate natural  milk  from  a  physical  po  nt  of  view.  Bos- 
worth has  carried  out  successful  feeding  experiments  on 
infants  with  milks  thus  prepared. 

Bosworth  informed  us  that  his  method  was  beset  with 
certain  difficulties  which  were  finally  overcome.  It  proved 
not  always  easy  to  get  the  fat  properly  emulsified.  What 
has  been  said  in  these  pages  regarding  the  mechanical  and 
concentration  conditions  which  must  be  met  in  order  to 
prepare  emulsions  successfully,  contains,  we  think,  the  an- 
swer to  his  difficulties.  His  method  of  producing  an  emul- 
sion by  homogenizing  his  fat  in  much  water  cannot  yield 
as  good  results  as  when  what  may  be  termed  the  more 
"natural"  method  is  followed  of  first  dividing  the  fat  into 
a  rather  highly  concentrated  hydrated  colloid  and  then 
diluting  the  resulting  mixture. 

1  A.  W.  Bosworth:  Personal  Communication,  April,  1916. 


NATURAL  AND  ARTIFICIAL  PRODUCTION  OF  MILK      109 

In  our  own  method  of  making  artificial  milk,  we  begin 
with  the  hydratable  colloids  that  are  to  appear  in  the 
finished  product.  If  cow's  milk  is  to  be  imitated,  we  start 
with  pure  (amphoteric)  cow's  casein  to  which  enough  alkali 
is  added  to  produce 
neutralization  of  the 
protein  and  only  just 
enough  water  to  furnish 
the  optimum  concentra- 
tion for  the  division  of 
the  fat  in  it.  For  pure 
casein,  with  pure  so- 
dium carbonate  as  the 
alkali,  and  with  dis- 
tilled water,  this  point 
is  reached  when  each 
gram  of  protein  has 
0.4  cc.  molar  sodium 
carbonate  added  to  it; 
but  the  presence  of 
other  proteins,  of  other 
salts,  etc.,  in  the  mix- 
ture at  once  changes 
this  relation  of  the  dif- 
ferent elements  to  each 
other,  and  so  the  new 
optimum  point  must  be 
discovered  for  each 
new  mixture.  The  best 
guide  as  to  when  the 
right  point  is  reached  is 

found  in  the  pecuUar  crackling  noise,  so  often  noted  by 
workers  on  the  emulsions,  produced  whenever  the  hy- 
dration of  the  protein  has  been  carried  to  the  right  point. 
The  danger  of  getting  poor  results  is  greater  when  too 
much  water  is  added  than  when  the  opposite  is  done. 
Once  a  concentrated  emulsion  of  fat  in  hydrated  casein  has 


no 


FATS  AND  FATTY   DEGENERATION 


been  produced,  it  is  an  easy  matter  to  dilute  it,  to  add  other 
proteins  (like  lact-albumin  and  lact-globulin)  and  finally  the 
salts  and  the  milk  sugar  to  obtain  the  emulsion  which  will 
ultimately  have  all  the  physical  and  chemical  properties  of 
cow's  milk  or  of  any  other.     An  artificial  cow's   milk  in 


Fig.  46. 

which  oleomargarin  has  replaced  the  ordinary  ''butter"  fat 
is  shown  in  Figure  45. 

This  general  procedure  may  be  varied,  of  course,  to  suit 
different  circumstances.  One  may  begin  with  other  pro- 
teins of  milk  instead  of  the  casein,  or  with  the  whole  set 
together  which  is  found  in  the  milk.  Or  other  proteins 
may  be  used  instead  of  the  normal  proteins  of  milk  and  so 


NATURAL  AND  ARTIFICIAL  PRODUCTION  OF  MILK      111 

mixtures  physically  identical  with  mammalian  milks  but 
of  a  different  chemical  composition  may  be  produced.  In 
place  of  the  normal  proteins  of  milk,  we  have  in  this  way 
used  the  proteins  of  egg,  of  blood  and  of  muscle.  ''Milks" 
produced  with  the  proteins  of  the  first  two  are  shown  in 
Figure  46.  We  have  also  used  gelatin,  and  since  the  hy- 
drophilic  character  of  the  colloid  is  the  essentially  important 
element,  we  have  made  ''milks''  of  soap  and  of  carbohy- 
drates (dextrin).  In  place  of  butter-fat  or  oleomargarin, 
lard  may  be  used,  or  other  animal  fats,  or  cottonseed  oil 
including  its  hydrogenated  derivatives. 

From  a  physical  point  of  view,  there  is  no  difficulty  in 
replacing  the  animal  or  vegetable  fats  through  mineral  oils; 
and  the  salts  or  sugars  that  we  may  care  to  put  into  a  milk 
offer  wide  realms  of  choice  both  as  to  character  and  con- 
centration. 


VIII.  ON  THE  MIMICRY  OF  MUCOID 
SECRETION. 


VIII.   ON  THE  MIMICRY  OF  MUCOID 
SECRETION. 

The  following  observations  made  in  the  course  of  our 
study  of  the  formation  and  the  breaking  of  emulsions  have 
so  much  to  do  with  a  possible  understanding  of  the  ways 
and  means  by  which  the  mucoid  secretions  are  formed  upon 
the  mucous  surfaces  that  a  few  paragraphs  regarding  them 
seem  justified. 

§1. 

In  the  steady  growth  of  the  successful  re-analysis  of 
biological  behavior  in  the  terms  of  colloid  chemistry,  sev- 
eral of  the  phenomena  associated  with  the  formation  of  the 
mucoid  secretions  present  difficulties.  In  the  case  of  the 
essentially  aqueous  secretions  like  urine  and  sweat,  it  seems 
fairly  well  settled  that  they  are  not  given  off  ''as  such'' 
but  are  divisible  into  two  phases :  —  the  secretion  of  water 
and  the  secretion  of  dissolved  substances.^  The  secretion 
of  water  is  primary,  while  a  leaching  out  by  the  water  of 
the  various  dissolved  substances  found  in  the  secreting  cells 
follows  secondarily.  The  combined  process  yields  the  com- 
pleted secretion.  But  the  dissolved  substances  in  these 
instances  are  crystalloid  in  character ;  in  other  words,  readily 
capable  of  passing  into  and  through  the  colloid  membrane 
which  is  constituted  by  the  cells  making  up  the  secreting 
parenchyma.  When  certain  colloids  appear  in  the  secre- 
tions, as  when  albumin  appears  in  the  urine,  the  problem 
may  still  remain  relatively  simple,  for  under  the  conditions 
which  lead  to  albuminuria  it  is  easily  possible  to  discover 
agencies  at  work  —  such  as  the  production  or  accumula- 

1  See  Martin  H.  Fischer:  (Edema  and  Nephritis,  32i  and  512.  Second 
edition,  New  York,  1915.  There  references  to  the  original  studies  may  be 
found. 

115 


116         FATS  AND  FATTY  DEGENERATION 

tion  of  acids,  of  urea,  or  of  various  amins  —  which  render 
more  diffusible  the  ordinarily  non-diffusible  proteins  of  the 
kidney.  But  this  explanation  proves  inadequate  when  we 
come  to  secretions  of  the  mucoid  type. 

Since  the  mucins  are  highly  colloid,  it  is  not  only  difficult 
to  see  how,  through  processes  of  diffusion  alone,  they  get 
out  of  the  cells  in  which  they  are  formed  into  the  secretions 
themselves,  but  the  problem  is  further  complicated  by  the 
fact  that  the  mucoid  secretions  may  be  so  thick  • —  one 
needs  but  to  think  of  the  tenacious  secretions  of  certain 
plants,  or  of  the  discharges  from  the  respiratory  passages 
or  the  alimentary  tract  in  certain  physiological  and  patho- 
logical conditions  —  that  one  cannot  believe  that  the  secre- 
tions ever  came  ready-made  in  so  highly  hydrated  a  form 
from  the  cells  themselves. 

In  an  attempt  to  explain  the  matter  physico-chemically, 
it  has  been  suggested^  that  in  these  mucoid  secretions 
practically  non-hydrated  (unswollen)  colloids  are  first 
pushed  off  by  the  mucous  cells  upon  their  surfaces,  and  that 
these  swell  subsequently  when  water  becomes  available, 
either  through  the  secretion  of  water  by  the  cells  themselves, 
or  from  without. 

§2. 

In  the  following  model  much  that  is  analogous  to  this 
idea  of  their  formation  and  much  that  is  applicable,  in  con- 
sequence, to  the  mechanism  of  the  formation  of  these  mu- 
coid secretions  both  in  plants  and  in  animals,  is  not  only  to 
be  observed  directly,  but  since  the  observed  phenomena 
are  capable  of  analysis  in  the  terms  of  physical  and  colloid 
chemistry,  the  possibility  is  tacitly  suggested  that  the  an- 
alogous biological  phenomena  may  also  some  day  be  simi- 
larly analyzed. 

To  simulate  the  protoplasm  of  mucous  cells,  a  mixture 
is  made  in  a  mortar  of  a  small  amount  of  powdered  gum  of 

^  Martin  H.  Fischer:  Physiology  of  Alimentation,  187,  New  York, 
1907. 


ON  THE  MIMICRY  OF  MUCOID  SECRETION  117 

acacia  in  a  cubic  centimeter  or  two  of  cottonseed  oil.  Such 
a  mixture  after  being  thoroughly  triturated  appears  under 
the  microscope  as  a  continuous  oil  layer  in  which  the  jagged 
particles  of  broken  acacia  are  readily  visible  (Figure  47). 


Fig.  47. 


Fig.  48. 


If  now  a  drop  of  water  is  allowed  to  touch  the  edge  of  this 
oil  layer,  an  interesting  set  of  changes  occurs.  The  oil 
edge  is  observed  to  show  surface  motions  (surface  tension 
movements)  and  the  acacia  particles  within  the  oil  mass 
are  rapidly  carried  to  the  surface  of  the  oil  and  extruded 
(Figure  48).  Such  extrusion  is  entirely  analogous  to  the 
extrusion  of  foreign  substances  —  such  as  ink  particles,  car- 


118  FATS  AND  FATTY  DEGENERATION 

mine  particles,  or  other  substances  —  by  living  cells.  The 
particles  of  acacia  as  soon  as  extruded  from  the  oil  ''dis- 
solve" in  the  water  covering  the  oil  and  in  so  doing,  cover 
the  oil  with  a  tenacious,  mucoid  mass. 

The  ''solution"  of  the  acacia  particles  is  not  only  readily 
observable  microscopically  but  may  be  observed  macro- 
scopically  in  the  rather  rapid  thickening  of  any  water 
brought  in  contact  with  the  acacia-oil  mixture. 

While  the  oil  which  contains  the  acacia  particles  may  not 
be  compared  directly  to  protoplasm  from  a  chemical  point  of 
view,  it  does  in  its  "liquid"  behavior  act  like  it  physically. 
Protoplasm,  too,  is  best  conceived  of  as  a  physical  mixture 
of  several  mutually  immiscible  liquids. 


§3. 

The  observations  detailed  here  may  perhaps  serve  not 
only  for  the  demonstration  in  class  of  phenomena  in  "non- 
living" matter  strikingly  like  those  observable  in  living 
cells,  but  in  so  doing  may  suggest  also  the  analysis  of  such 
"living"  phenomena  in  the  terms  of  surface  tension,  solu- 
bility, etc. 


IX.   ON  THE  MIMICRY  OF   SOME  ANATOMICAL 
STRUCTURES. 


IX.  ON  THE  MIMICRY  OF  SOME  ANATOMICAL 
STRUCTURES. 

I.  INTRODUCTION. 

§1. 

The  history  of  anatomy  may  be  divided  into  two  parts: 
a  morphological  division  and  a  physiological  one.  Under 
the  former  heading,  description  has  been  an  end  in  itself; 
under  the  latter,  this  has  been  supplemented  by  an  inquiry 
regarding  why  the  structure  has  come  to  pass.  The  older 
gross  morphological  anatomy  with  its  attendant  gross  phys- 
iology began  to  give  way,  in  the  middle  of  the  last  century, 
to  a  cellular  anatomy  and  a  cellular  physiology,  a  develop- 
ment which  culminated  in  that  ultra-refinement  of  anatom- 
ical and  physiological  analysis  of  the  last  decade  which 
describes  the  internal  structures  of  cells  themselves  and 
of  the  protoplasm  constituting  them.  Names  inseparably 
connected  with  this  newest  but  most  important  school  of 
physiological  anatomy  are  those  of  Walther  Flemming,^ 
O.  BtJTSCHLi,-  Alfred  Fischer,^  W.  B.  Hardy  ^  and  C.  B. 
Davenport.^ 

These  paragraphs  merely  add  to  the  studies  of  these 
observers,  being  of  interest  chiefly  in  that  they  show  how 
from  simple  colloids  and  colloid  mixtures  exposed  to  slightly 
varying  external  conditions  (as  expressed,  for  example,  in 
the  removal  or  addition  of  water)  complex  morphological 
pictures  result  which  are  strikingly  like  those  observed  in 
the  anatomical  structures  characteristic  of  Uving  matter. 

1  Walther  Flemming:  Zellsubstanz,  Kern  und  Zelltheilung,  Leipzig, 
1882. 

2  O.  BtJTSCHLi:  Untersuchimgen  iiber  Structuren,  Leipzig,  1898. 

3  Alfred  Fischer:  Fixirung,  Farbiing  und  Bau  des  Protoplasmas,  Jena, 
1899. 

<  W.  B.  Hardy:  Proc.  Roy.  Soc.,  66,  95  (1899);  Am.  Jour.  Physical  Cbem., 
4,  254  (1900);  Zeitschr.  f.  physik.  Chem.,  33,  326  (1900). 

'  C.  B.  Davenport:  Experimental  Morphology,  New  York,  1908. 

121 


122  FATS  AND  FATTY   DEGENERATION 

§2. 

As  generally  recognized  by  the  experimental  morpholo- 
gists,  the  problem  of  growth  may  be  divided  into  two 
parts:  a  first,  which  may  be  regarded  as  growth  proper  and 
a  second  which  is  best  discussed  under  the  heading  differ- 
entiation. The  former  is  best  defined  as  an  increase  in 
volume  which,  as  we  have  previously  pointed  out,^  is  best 
conceived  of  as  due  to  an  increased  swelling  of  the  affected 
cell,  tissue  or  organ  undergoing  growth.  This  increase  in 
volume,  which  is  generally  looked  upon  as  a  ^'second  stage" 
in  growth,  is  secondary  to  a  ^' first  stage"  which  in  its 
turn  consists  of  a  laying  down  of  colloid  materials,  or  of  a 
change  in  conditions  siu-rounding  such  as  have  been  laid 
down  which  make  these  absorb  an  increased  amount  of 
water. 

We  have  also  emphasized  how,  through  inequalities  in 
the  amount  of  water  thus  absorbed,  stresses  and  strains  are 
induced  within  the  growing  (swelling)  colloid  masses  con- 
stituting the  individual  cells  or  organs,  which  lead  to  the 
production  of  ciu-vatures  in  them,  commonly  known  as 
growth  curvatures  and  generally  held  to  represent  a  re- 
sponse to  certain  chemical  changes  occurring  within  the 
protoplasm  itself,  or  to  such  as  are  produced  in  the  proto- 
plasm through  the  various  'Hropisms"  to  which  growing 
plants  (Sachs)  or  animals  (Loeb)  may  be  subject. 

But  not  only  may  growth  proper  —  as  well  as  certain  in- 
equalities in  growth  which  we  have  thus  far  touched  upon 
and  which  already  bring  with  them  the  first  elements  of 
differentiation  —  be  thus  interpreted  in  the  terms  of  colloid 
chemistry,  but  even  those  very,  complicated  cellular  changes 
which  are  more  readily  accepted  under  the  term  differen- 
tiation may  be  thus  understood.  Some  years  ago  Fischer 
and  Wolfgang  Ostwald  ^  pointed  out  that  so  complicated 

1  Martin  H.  Fischer:  Pfluger's  Arch.,  124,  70  (1908);  ibid.,  125,  99 
(1908);  (Edema  and  Nephritis,  372,  2nd  Edition,  New  York,  1915. 

2  Martin  H.  Fischer  and  Wolfgang  Ostwald:  Pfluger's  Arch.,  106, 
229  (1905). 


THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES      123 

an  example  of  cell  differentiation  as  astrophere  formation 
may  safely  be  defined  as  a  localized  and  oriented  gel  formation. 

§3. 

In  the  com-se  of  these  studies  on  emulsions,  we  were 
frequently  struck  by  the  complexity  of  the  structures  pro- 
duced when  emulsions  are  subjected  to  the  simple  process 
of  drying,  to  increases  in  concentration  of  the  one  phase  or 
the  other,  to  the  addition  of  water,  the  addition  of  various 
extraneous  substances,  etc. 

These  pages  would  present  through  photographs  a  few  of 
the  structures  thus  observed  and  state  the  conditions  under 
which  they  were  obtained.  The  similarity  between  them 
and  certain  histological  pictures  is  so  striking  that  one  can- 
not avoid  the  conclusion  that  the  nature  of  the  forces  pro- 
ducing each  must  be  very  similar;  and  since  in  the  forma- 
tion of  even  the  most  complex  of  the  structures  reproduced 
herewith,  we  know  the  forces  concerned  to  be  relatively 
simple  in  character  and  capable  of  analysis,  it  seems  prob- 
able that  the  explanation  of  the  mechanism  by  which 
similar  forms  observed  in  living  matter  are  produced  is 
likely  to  prove  equally  simple. 

2.   ON  THE  MIMICRY  OF  CERTAIN  ANATOMICAL 
STRUCTURES. 

§1. 

It  is  fairly  well  settled  and  quite  generally  accepted  that 
all  of  the  three  allegedly  fundamental  structures  compos- 
ing protoplasm  itself  —  the  granular,  the  fibrillar,  the  honey- 
comb —  are  merely  expressions  of  inclusion  or  separation 
phenomena  in  a  previously  homogeneous  phase.  When, 
for  example,  in  one  optically  homogeneous  Hquid  phase,  a 
second  liquid  is  divided  which  has  a  different  index  of  re- 
fraction, or  when  in  a  previously  homogeneous  liquid  phase 
the  second  is  made  to  appear  which  has  a  different  index  of 
refraction,  a  granular  structure  results. 


124 


FATS  AND   FATTY   DEGENERATION 


Fig.  49. 


Fig.  50. 


THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES      125 

This  phenomenon  is  readily  observable  in  optically  homo- 
geneous soap  solutions  (like  25  percent  potassiimi  soap  in 
water)  when  a  very  dilute  acid  (like  the  fumes  of  the  labo- 
ratory or  a  y^  normal  acid  of  any  sort)  is  permitted  to  dif- 
fuse into  them.  When  this  occurs,  the  previously  clear  soap 
(because  of  a  separation  of  the  insoluble  fatty  acid)  be- 
comes opalescent  or  milky  and,  on  examination  under  the 
highest  powers  of  the  microscope,  is  seen  to  teem  with 


^    n       '^ 


•%^^^^^:^^-^-:^-x 


13 


Fig.  51. 


minute  refractile  bodies  in  active  Brownian  movement,  as 
shown  in  Figure  49.  From  this  originally  highly  dispersed 
granular  structure  there  evolves  a  coarser  one,  as  shown  in 
Figure  50,  if  the  acid-treated  soap  is  left  to  itself  for  a  time; 
and  in  the  course  of  some  hom^  or  days,  such  a  coarse 
emulsion  of  fatty  acid  in  salt  water  as  is  shown  in  Figure  51 
results. 

If  the  experiment  is  carried  on  macroscopically,  a  con- 
tinuous layer  of  fatty  acid  is  likely  to  accumulate  above 
the  aqueous  phase. 

When  such  separation  of  fatty  acid  from  soap  is  car- 


126 


FATS  AND  FATTY  DEGENERATION 


ried  out  under  conditions  which  do  not  destroy  the  hy- 
drophihc  nature  of  the  hquid  medium  surrounding  the  fatty 
acid  droplets,  the  minute  fatty  acid  granules  remain  in 
finely  divided  form.     This  can  be  accomplished,  for  ex- 


FiG.  52. 

ample,  by  mixing  the  original  soap  solution  with  gelatin, 
when  a  more  lasting  picture  of  the  type  shown  in  Figure  49 
is  obtained. 

§2. 

When  the  separation  of  one  liquid  phase  in  a  second,  as 
that  of  fatty  acid  in  an  aqueous  dispersion  medium,  is  per- 
mitted to  occur  in  solutions  of  proper  composition  and  con- 


THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES      127 

centration  (hydrated  colloids  of  high  concentration,  hke 
concentrated  soaps),  the  separating  phase  may  yield  enough 
non-coalescing  globules  to  make  up  most  of  the  field.     This 


Fig.  53. 


picture  is  produced  when  concentrated  soaps  are  treated 
with  acid.  It  may  also  be  produced  when  a  gas,  like  air, 
is  beaten  into  a  soap  solution  to  make  a  foam.  Under  such 
circumstances,  mutual  pressures  result  which  deform  the 
originally  spherical  globules  of  fatty  acid  or  air  and  such 


128 


FATS  AND  FATTY   DEGENERATION 


honej^comb  structures  form  as  are  illustrated  in  Figure  52. 
Such  structures,  which  have  been  brilliantly  described  by 
BtJTSCHLi,  remind  one  not  only  of  the  fundamental  honey- 


FiG.  54. 

comb  structure  observed  in  protoplasm  itself,  but  of  those 
coarser  honeycomb  structures  which  may  be  observed  in 
the  alveolar  structure  of  the  organs  of  various  mammals. 
Figure  52,  for  example,  looks  not  unlike  a  microscopic 
section  of  lung. 


THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES      129 

§3. 

In  Figure  53  is  shown  the  microscopic  appearance  pro- 
duced in  the  drying  of  an  oil-in-soap  (25  percent  potassium 
soap)  emulsion.  Of  interest  here  are  the  "protoplasmic 
bridges"  (of  soap)  formed  between  the  shrinking  fragments 
of  emulsion.  These  bridges  are  not  unlike  those  seen  his- 
tologically in  materials  derived  from  hving  sources.  When 
very  fine,  these  bridges  are  not  unlike  the  bridges  observed 
between  the  epithelial  cells  (prickle  cells)  of  the  skin.  In 
coarser  form,  especially  when  globules  of  oil  become  en- 
meshed in  them,  they  remind  one  of  the  rods  and  cones  of 
the  retina,  as  illustrated  in  Figure  54. 


§4. 

A  protoplasmic  structure  combining  the  fibrillar  and 
granular  is  shown  in  Figure  55.  A  fibrillar  structure  com- 
posed of  granules  arranged  in  threads  is  often  referred  to 


130  FATS  AND  FATTY  DEGENERATION 


Fig.  56. 


Fig.  57. 


THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES     131 


Fig.  58. 


132  FATS  AND  FATTY  DEGENERATION 

in  the  text-books  of  histology.  The  original  matrix  for 
Figure  55  is  a  partially  swollen  mixture  of  acacia  and  dried 
egg-white.  When  a  little  dilute  acid  is  allowed  to  diffuse 
into  a  drop  of  this  material  under  a  cover  slip,  the  originally 
fairly  homogeneous  mixture  not  only  begins  to  swell  but 
some  of  the  proteins  (the  globulins)  of  the  egg-white  are 
precipitated  as  tiny  granules.  These  tend  to  accumulate 
in  the  acacia  threads  which  are  being  dragged  through  the 
swelling  mass  and  so  the  appearance  of  such  granular  threads 
as  are  shown  in  Figure  55  comes  about. 

§5. 

When  a  mixture  of  two  partially  hydrated  colloids  (just 
such  mixtures  as  are  formed  in  those  parts  of  plants  and 
animals  which  are  in  the  so-called  first  stage  of  growth) 
like  acacia  and  egg  albumin  is  permitted  to  swell  further 
through  the  addition  of  a  little  water,  stresses  and  strains 
occur  in  the  swelling  mixture,  owing  to  the  differences  in 
the  indices  of  swelhng  of  the  two  colloids,  which  yield 
interesting  morphological  results.  (Such  increased  imbibi- 
tion of  water  corresponds,  as  is  well  known,  to  the  second 
stage  of  growth.)  The  edge  of  such  a  swelling  mass  is  shown 
in  Figure  56.  The  projections  forming  at  the  free  surface 
of  the  mixture  remind  one  strongly  of  the  nodules  which 
mark  the  first  evidences  of  the  formation  of  new  organs  in 
embryos,  of  the  mucous  membrane  tufts  (villi)  of  the  in- 
testine, etc. 

§6. 

But  the  deeper  portions  of  such  a  picture  as  is  shown  in 
Figure  56  are  also  of  interest.  The  stresses  and  strains 
incident  to  the  unequal  swelling  of  the  acacia  and  the  pro- 
tein yield  interesting  structures  here  also.  As  Figure  57 
shows,  structures  that  remind  one  strongly  of  embryonic 
connective  tissue,  of  rapidly  growing  involuntary  muscle 
cells,  of  the  appearance  of  fibromas,  myomas  and  sarcomas, 


THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES     133 

etc.,  are  produced.  Even  when  highly  magnified  (850  di- 
ameters), as  shown  in  Figure  58,  this  appearance  is  not 
destroyed. 

§7. 

The  fine  markings  which  we  observe  in  our  skins  (in 
their  purest  form,  in  those  portions  which  are  distant  from 
joints  and  not  subject  to  direct  creasing)  seem  also  to  be 
but  the  expression  of  the  effects  of  drying  in  hydrated 
colloids.  Structm-es  similar  to  these  skin  figures  may  be 
observed  in  drying  proteins  like  egg-white  as  first  described 
by  O.  BuTSCHLi.^  When  thin  layers  of  egg  albumin  are 
spread  upon  a  glass  slide  and  left  to  dry  in  the  air,  Unear 
crackings  occur  as  shown  in  Figures  59  and  60.  These 
linear  cleavages  remind  one  not  only  of  the  linear  crackings 
observable  in  our  own  skins  but  in  many  other  drying  ani- 
mal and  plant  tissues.  Under  higher  magnifications  of  the 
microscope  they  present  the  appearance  seen  in  Figure  61. 

It  is  only  necessary  to  increase  the  thickness  of  the  dry- 
ing egg  white  film  to  have  these  essentially  linear  crackings 
give  rise  to  more  complicated  structures  such  as  are  shown 
in  Figure  62.  In  addition  to  the  linear  crackings,  there  now 
occur  large  numbers  of  transverse  ones  which  yield  poly- 
gons of  various  sizes  and  shapes.  But  in  addition  to  the 
formation  of  these  polygons,  secondary  inspissation  figures 
of  great  beauty  begin  to  appear  within  many  of  them. 
While  observable  in  Figure  62,  they  are  more  clearly  dem- 
onstrated at  somewhat  higher  magnification,  as  shown  in 
Figure  63  or  in  Figure  64  which  is  magnified  850  diam- 
eters. 

All  these  linear,  polygonal  and  circular  inspissation  fig- 
ures may  be  seen  in  the  normal  skin,  but  the  last  of  them 
reminds  one  most  definitely,  perhaps,  of  figures  observable 
macroscopically  or  microscopically  in  certain  skin  diseases 
which  are  associated  with  a  thickening  of  the  epithelial 
structures  and  their  abnormal  drying.     The  circular  inspis- 

^  O.  BiJTSCHLi:   Untersuchungen  iiber  Strukturen,  34,  Leipzig,  1898. 


134 


FATS  AND  FATTY  DEGENERATION 


Fig.  59. 


Fig.  60. 


THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES      135 


136 


FATS  AND  FATTY  DEGENERATION 


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THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES      137 


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138 


FATS  AND  FATTY   DEGENERATION 


sation  figures  also  bring  to  mind  the  appearances  charac- 
teristic of  certain  cancers  (epithehomas)  when  these  are 
studded  with  ''whorls"  or  ''pearls/' 


Fig.  64. 


3.   ON   THE   PROTECTIVE  COVERINGS   OF  PLANTS. 

In  concluding  these  descriptions  of  microscopic  and  mac- 
roscopic structures  as  produced  in  the  processes  of  hydra- 
tion and  dehydration  of  individual  and  mixed  hydrated 
colloids,  we  should  like  to  draw  attention  to  a  finding  pre- 
viously commented  upon.^  As  emphasized  there,  an  oil- 
in-hydrated  protein  emulsion  tends  on  simple  drying  to 

^  See  page  52. 


THE  MIMICRY  OF  SOME  ANATOMICAL  STRUCTURES      139 

pass  over  into  a  hydrated  protein-in-oil  type.  The  process 
may  be  observed,  for  example,  in  the  drying  surface  of 
ordinary  egg  yolk.  The  beads  of  oil  which  form  upon  the 
surface  are  shown  in  the  field  b  of  Figure  65.  As  the  oil 
droplets  increase  in  number  they  tend  to  coalesce  and  to 
form  a  continuous  film.  If  the  oil  is  of  a  drying  type,  a 
continuous  oil  film  forms  over  the  siuface  of  the  emulsion. 
Such  a  continuous  oil  film  is  shown  in  the  field  a  of  Figure 
65.     We  emphasize  these  changes  and  the  appearances  thus 


Fig.  65. 

produced  because  we  believe  they  explain  not  only  the 
mechanism  but  also  the  appearance  characteristic  of  similar 
structures  seen  in  flowers,  leaves,  fruits,  etc.  Not  only 
are  the  surfaces  of  many  flowers,  for  instance,  studded 
with  minute  oil  droplets,  but  in  many  flowers  and,  still 
better,  in  many  leaves  and  fruits,  such  droplets  may  be 
observed  to  coalesce  (with  subsequent  drying  of  the  oil)  to 
form  the  shiny,  continuous  oil  films  covering  these  struc- 
tures.^ 


^  If,  as  the  conversion  of  the  oil-in-water  emulsion  to  the  water-in-oil 
type  occurs  upon  the  surface  of  a  fruit,  for  example,  there  remains  behind 
on  the  surface  of  the  oil  film  a  drying  protein,  silicate  or  other  material,  then 
the  fruit  becomes  covered  with  a  "bloom." 


140  FATS  AND  FATTY  DEGENERATION 

The  importance  of  these  waterproof  films  (in  the  case  of 
leaves,  for  example)  is  self-apparent.  Were  plants  not  pos- 
sessed of  them,  every  rain  would  destroy  them.  The  water- 
in-oil  type  of  emulsion  protects  the  plant  against  the  effects 
of  rain  from  without ;  the  oil-in-water  type  within  the  plant 
allows  it  to  imbibe  this  same  water  from  the  soil  after  the 
rain  has  fallen. 


X.  CONCLUDING  PARAGRAPHS. 


X.   CONCLUDING  PARAGRAPHS. 

§1. 

If,  in  retrospect,  we  try  to  state  the  value  of  the  preceding 
pages,  we  may  say  that  they  represent  an  attempt  to  ana- 
lyze colloid-chemically  the  third  phase  in  the  reaction  of 
living  matter  to  injury.  We  did  not  anticipate  such  a 
finding  when  we  began  our  studies,  but  this  conclusion  is 
nevertheless  forced  upon  us. 

The  one  universal  element  in  that  reaction  of  living  matter 
to  injury,  which  is  called  inflammation,  is  a  swelling  of  the 
injured  part.  This  is  also  the  first  phase  in  the  reaction. 
In  the  terms  of  colloid  chemistry,  we  have  defined  this 
swelling  as  an  increased  hydration  capacity  of  the  tissue 
colloids.  If  the  conditions  causing  the  inflammatory  reac- 
tion are  sufficiently  severe  and  sufficiently  lasting,  a  *' cloud- 
ing" of  the  swollen  tissues  takes  place,  the  two  together 
yielding  '^  cloudy  swelling."  This  clouding  we  have  defined 
as  a  dehydration  with  consequent  precipitation  of  a  second 
group  of  the  tissue  colloids  within  the  mass  of  the  previ- 
ously discussed  swelling  ones.  Accompanying  this  second 
stage  in  inflanmiation  or  following  it  comes  that  third  stage 
with  which  these  pages  have  chiefly  dealt,  namely  that  of 
'  ^  fatty  degeneration. ' ' 

When  we  parallel  these  three  stages  with  the  altered 
function  which  accompanies  the  ^^nflanomatory"  reaction 
to  injury,  we  note  that  even  the  first  stage  may  be  accom- 
panied by  much  disturbance,  that  the  second  may  show 
this  in  extreme  form  and  that  the  third  may  show  a  com- 
plete loss  of  the  characteristic  functions  of  the  involved 
tissues.  We  emphasize  these  facts  because  the  orthodox 
pathologists  pass  rather  lightly  over  these  first  morphological 
evidences  of  injury  which  in  their  terms  are  mere  ^'albu- 

143 


144  FATS  AND  FATTY  DEGENERATION 

minous"  and  ''fatty  degenerations."  And  yet  if  it  is  but 
remembered  that  function  and  not  morphological  pathology 
is  the  matter  of  real  interest  to  the  worker  in  medicine 
and  biology,  it  will  at  once  be  seen  that  all  the  changes  in 
living  tissues  beyond  these  first  and  largely  ignored  ones 
are  of  a  type  of  more  interest  in  the  dead  house  than  to 
the  still  living  host  that  harbors  them. 

The  reasons  for  these  obvious  conclusions  exist  in  the 
possibilities  and  non-possibilities  for  the  reversal  of  the  proc- 
ess in  these  three  states.  The  changes  incident  to  the 
mere  swelling  of  the  first  stage  are  still  quite  readily  revers- 
ible; even  those  of  the  second  or  clouding  stage  are  still 
largely  reversible,  but  more  slowly.  The  fatty  changes 
characteristic  of  the  third  mark  the  transition  point  to 
the  final  or  fourth  and  irreversible  stage  of  necrosis  (the 
stage  of  the  irreversible  precipitation  or  '' coagulation '^  of 
the  protein  colloids  of  the  affected  tissues). 

While  a  cell  which  has  suffered  a  ''fatty  degeneration'^ 
may  still  recover,  it  is  scarcely  able  to  do  this  through  mere 
reversal  of  the  conditions  which  have  brought  about  the 
pathological  state.  Under  the  conditions  prevailing  within 
our  bodies,  for  example,  many  of  the  changes  characteristic 
of  fatty  degeneration  are  already  on  the  edge  of  the  irre- 
versible and  so  mark  the  dividing  line  between  the  living 
and  the  dead.  Even  when  the  normally  very  finely  divided 
oil  droplets  of  our  cells  have  coalesced  into  the  larger,  more 
readily  visible  ones  of  "fatty  degeneration,'^  the  fat  has 
already  passed  into  a  state  in  which,  on  reversal  of  the  con- 
ditions which  made  for  the  degeneration,  it  will  not  go 
back  into  the  finely  divided  form.  But  if  the  state  of  the 
fat  is  not  of  fundamental  importance  for  the  continuance 
of  the  living  state  of  the  cell  and  if  those  changes  (the 
cloudy  swelling)  within  the  cell  which  affect  the  proteins, 
for  example,  are  still  reversible,  the  cell  as  a  whole  may  go 
on  living.  Complete  restitution  to  the  normal,  however, 
can  only  be  effected  by  indirect  means.  There  is  no  ma- 
chine which  in  our  bodies,  as  in  our  laboratories,  will  sub- 


CONCLUDING  PARAGRAPHS  145 

divide  again  the  fat;  but  nature  can,  by  digestion  of  the 
fat  to  fatty  acid  and  glycerin  and  their  redeposition  as  fat  in 
the  normal  finely  divided  form,  bring  about  the  original 
state  of  the  cell.  In  this  way  the  first  stages  of  '^ fatty  de- 
generation" still  remain  of  an  ultimately  reversible  type. 
But  except  as  such  digestion  with  redeposition  of  the  fat 
is  still  possible,  even  the  mere  coalescence  of  the  small  fat 
droplets  into  the  larger  ones  represents  in  our  bodies  a 
practically  irreversible  physical  change.  And  once  this 
coalition  of  the  fat  droplets  has  gone  to  the  point  of  gross 
separation  (accompanied  by  the  great  dehydration  and  pre- 
cipitation of  the  cell  proteins  with  its  accompanying  sep- 
aration of  water  which  we  call  ^4issue  softening")  the  proc- 
ess is  absolutely  irreversible  and  the  death  of  the  part 
(necrosis)  is  at  hand.  In  om*  laboratories  we  can  again 
rebuild  our  original  system,  but  in  a  brain,  in  a  cut  nerve, 
or  in  a  parenchymatous  organ  this  is  out  of  the  realm  of 
the  possible.  Nature  can  repair  the  defect  only  as  she 
builds  new  tissues  into  the  stricken  area. 

§2. 

We  have  frequently  been  asked  what  is  the  bearing  of 
these  pages  upon  the  practical  problems  of  chemistry,  of 
biology  and  of  medicine. 

It  need  not  be  emphasized  that  they  replace  with  definite 
laws  much  of  what  was  empirical  in  the  production,  main- 
tenance and  destruction  of  the  emulsions  as  these  appear  to 
the  pharmaceutical  chemist,  the  purveyor  of  food,  the  dairy- 
man, or  the  manufacturer  of  rubber,  lubricating  materials, 
or  soap  products. 

To  those  biologists  and  physicians  whose  daily  endeavors 
are  not  tinged  with  imagination  or  contaminated  by  phil- 
osophy, these  pages  may  well  be  admitted  to  be  of  no  prac- 
tical worth  whatsoever.  To  the  others,  they  have  a  lim- 
ited value.  It  is  the  fundamental  duty  of  the  physician  to 
determine  how  many  of  the  changes  which  he  sees  in  the 


146  FATS  AND   FATTY  DEGENERATION 

ill  before  him  are  of  a  reversible  type  and  how  many  are 
irreversible.  Only  as  the  observed  changes  are  completely 
reversible  is  ^^cure"  possible.  The  eternal  debate  of  the 
value  of  therapeutic  procedures  seems  never  to  end.  Why 
need  the  fact  be  argued  that  any  '^disease"  treated  by  any 
therapeutic  scheme  whatsoever  might  have  '^gotten  well 
anyway"?  This  only  states  that  the  series  of  changes  from 
which  the  patient  suffered  were  still  of  a  reversible  type. 
But  only  changes  of  this  type,  and  no  others,  are  curable. 
The  important  function  of  the  physician  is  to  recognize  the 
fact,  and  then,  instead  of  leaving  the  job  to  nature  and 
chance,  aid  as  far  as  possible  in  estabUshing  the  reversal. 

In  the  stages  of  swelling  and  of  albuminous  degeneration 
we  are  already  far  into*  the  territory  of  altered  function; 
but,  as  we  have  previously  emphasized,  a  proper  recogni- 
tion of  the  nature  of  the  changes  before  us  gives  many  prac- 
tical hints  both  as  to  prevention  and  as  to  aid  toward 
reversal  of  these  changes.  In  the  problem  of  the  changes 
in  fat  distribution  within  cells  as  discussed  in  these  pages 
we  come  to  the  dividing  of  the  ways.  There  still  remains 
a  certain  margin  wherein  we  may  assist  nature  in  bringing 
about  reversal.  On  the  other  hand,  there  has  arrived  a 
dangerous  proximity  to  the  hne  of  the  irreversible.  For 
the  latter,  medicine  offers,  in  the  established  case,  only  the 
expedient  of  trying  to  make  the  irreparable  more  tolerable. 
But  such  a  better  understanding  of  our  biological  mecha- 
nisms still  brings  this  with  it.  If  it  does  not  teach  us  how  to 
repair  trouble,  it  at  least  emphasizes  the  importance  —  if 
the  owners  will  permit  it  —  of  advice  destined  to  keep  our 
biological  mechanisms  out  of  such  trouble.  And  that  seems 
to  be  the  heart  of  what  may  be  termed  the  new  medicine. 


INDEX 


AUTHOR  INDEX 


A. 

Araki,  T.,  75. 
Atwateb,  59,  91,  94. 

B. 
Bancroft,  Wilder  D.,  28,  29. 
Berman,  26. 
BiscHOFF,  E.,  57,  60. 
BoGGS,  Thomas  R.,  74. 
BOSWORTH,  A.  W.,  108. 
Bryant,  59,  91,  94. 
BUTSCHLI,  O.,  121,  13". 


Chevalier,  95. 
Chevalier,  Josephine,  60. 
Clowes,  G.  H.  A.,  28,  29,  30. 
Cahn,  59. 


K 

KoNiG,  J.,  59. 
Kraus,  F.,  81. 
KuPKA,  Josef,  22. 


Laptschinsky,  59. 
Lewis,  Wm.  C.  McC,  26. 
LoEB,  Jacques,  122. 
Liuenfeld,   59. 

M. 

Mallory,  F.  B.,  69. 
moleschott,  60. 
Moore,  B.,  61. 
Moore,  Gertrude,  51. 
Morris,  Roger  S.,  74. 


D. 

Davenport,  C.  B.,  121. 

F. 

Farwick,  B.,  59. 
Fischer,  Alfred,  121. 
Fischer,  Martin  H.,  26,  51,  61, 

75,76,115,116,122. 
Flemming,  Walther,  121. 
Friedleben,  59. 

G. 

Gierke,  E.,  69. 
Gorup-Besanez,  58,  89. 
Graham,  Evarts,  51,  74. 


64, 


Oesper,  26. 
Orgler,  a.,  84. 
Ostwald,  Walther,  21. 
OsTWALD,  Wolfgang,  20,  26,  122. 

P. 
Parke,  59. 
Perls,  89. 
Petrequin,  95. 
Petrowsky,  60. 
Pfluger,  E.,  67. 
Plateau,  S.,  27,  30. 
Pickering,  S.  U.,  28,  30,  53. 


H. 

Halliburton,  W.  D.,  59. 
Hardy,  W.  B.,   121. 
Hauser,  81. 
Hatschek,  Emil,  23. 
HlLLYER,  H.  W.,  28. 
Hoppe-Seyler,  F.,  59. 


Quincke,  G.,  27,  30. 

R. 
Ranke,  J.,  59. 
Robertson,  T.  B.,  21. 
Rosenfeld,  G.,  68,  69. 


149 


150 


AUTHOR  INDEX 


Rosenthal,  69. 
RuBOW,  v.,  84,  85. 


V. 

VmcHOW,  Rudolph,  67. 
VoiT,  Carl,  67. 


Sachs,  122. 
Salkowski,  59. 
SlEGERT,  F.,  84. 


W. 


Waldvogel,  84. 
Walter,  G.,  69. 


Taylor,  A.  E.,  69. 


Zawilsky,  59. 

ZiLLESSEN,  H.,  75. 


SUBJECT   INDEX 


A. 
Acacia,  30,  51. 
Acid,  7;  osmic,  9;   intoxication  by, 

10,  76;    effects  of,   on  emulsions, 

49,    51;     and   fatty   degeneration, 

75,85. 
Acid-casein,  6. 
Adipose  tissues,  11,  12,  89;   water  in, 

12;  as  water-in-fat  emulsions,  90. 
Adsorption,  53. 
Agar,  6,  31. 

Agents,  emulsifying,  6,  22,  26. 
Albumin,  blood,  6,  31. 
Albuminous  degeneration,  143,  144. 
Alcohol,  6,  8,  10,  50,  52. 
Aleuronat,  31. 

Alkali,  7;  efifects  of,  on  emulsions,  49. 
Alkali-casein,  6. 
Altered  function,  143. 
Alveolar  structure,  126. 
Anatomical  structures,   mimicry   of, 

121. 
Anemia,  74. 
Anesthetics,  50,  51,  52,  74,  76;   acid 

effects  of,  on  emulsions,  51. 
Animal  fats,  89. 
Argument,  the,  3. 
Arsenic,  10. 
Artificial  milk,  108.  109. 


B. 

Bile,  61,  62. 

Blood  albumin,  6,  31. 

Bloom  of  plants,  139. 

Brain,  9;  fatty  degeneration  in,  11; 

fat  in,  60. 
Breaking  of  emulsions,  7,  20,  47,  78, 

80. 
Bridges,  protoplasmic,  127,  129. 
Butter,  formation  of,  12,  20,  93,  94; 

physical  reactions  of,  94. 


C. 

Calcium  Soap,  49. 

Cane  sugar,  31,  44. 

Carbohydrates,  7,  61. 

Carbohydrate  emulsions,  51, 

Carcinomas,  138. 

Casein,  6,  31,  33,  35;  acid-,  6;  al- 
kali-, 6. 

Cell  membranes,  15,  63. 

Cells,  fat  in,  8,  57;  prickle,  129. 

Chloroform,  10,  50,  52. 

Churning,  93. 

Circulatory  disturbances,  10,  11,  75. 

Clearing  of  emulsions,  100. 

Cloudy  sweUing,  11,  76,  143;  in 
mammae,  106. 

Coagulation,  144. 

Coarsening  of  emulsions,  10. 

Colloidality,  44. 

Colloids,  hydrophiUc,  5;  dehydra- 
tion of,  7;  fat  in  hydrated,  11,  29, 
30;  secretion  of,  14, 115;  hydrated, 
6,  29;  solution  of,  32. 

Cones  and  rods  structure,  128. 

Connective  tissue  structure,  130,  131, 
132. 

Concentration,  effects  of,  on  emul- 
sions, 35,  37. 

Continuous  phase,  21. 

Cottonseed  oil,  4,  21,  25. 

Crackings,  linear,  133,  134. 

Critical  point  in  emulsions,  41. 

Crystalloids,  secretion  of,  115. 

Cure,  146. 

Cow's  milk,  artificial,  109. 

D. 

Death,  144. 

Definition  of  emulsions,  3,  4,  20; 
of  fatty  degeneration,  67;  of  fatty 
infiltration,  67,  68;  of  differen- 
tiation, 14,  122. 


151 


152 


SUBJECT  INDEX 


Degeneration,  Waller's,  76;  albu- 
minous, 143,  144;  fatty,  see  Fatty 
Degeneration. 

Dehydration,  effects  of,  on  emulsions, 
48;   of  colloids,  115. 

Deposition  of  fat,  19. 

Dextrin,  6,  33,  51. 

Diabetes,  10,  74. 

Differentiation,  14,  122. 

Dilution,  effects  of,  on  emulsions, 
13,  47,  53,  75. 

Diphasic  systems,  20. 

Disease,  146;  heart,  76;  vascular,  76. 

Dispersed  systems,  20. 

Dispersed  phase,  21. 

Dispersions,  gas,  27. 

Dispersoid,  5,  20. 

Distribution  between  two  phases,  53. 

Divided  phase,  21. 

Droplets,  subdivision  of,  23,  24. 

Drying,  of  egg  yolk,  99;  of  emul- 
sions, 52,  99;  structures  produced 
by,  133  to  138. 

E. 

Ear  Wax,  12,  95,  96. 

Edema,  143. 

Egg  white,  6,  31. 

Egg  yolk,  6,  20,  31;  drying,  99. 

Embolism,  76. 

Emulsifi cation,  4,  12;  concentration 
influence  in,  35;  hydrophilic  col- 
loids in,  34,  61;  methods,  5,  21,  22. 

Emulsifying  machines,  22. 

Emulsifying  agents,  6,  22,  26. 

Emulsions,  acid  effects  of  anes- 
thetics on,  51;  and  acid,  49;  and 
alkalies,  49;  breaking  of,  7,  20,  47, 
78;  carbohydrates,  51;  coarsen- 
ing of,  10;  clearing  of,  100;  and 
concentration,  37;  critical  point  in, 
41;  definition  of,  3,  4,  20;  de- 
hydration effects  on,  48;  dilution 
of,  13,  36,  47,  53,  75;  drying  of, 
52,  99;  experiments  on,  21;  fatty 
degeneration  in,  69;  fatty  tissues 
as  water-in-fat,  90;  colloids  as 
stabilizers  of,  61;    importance  of, 


3,  15,  145;  layers  in  breaking, 
39,  80;  making  of,  19,  20,  25, 
30;  microscopy  of,  41;  milk 
formation  from,  13;  oil  and  water, 
3,  21;  optical  changes  in,  12,  96, 
98,  100;  permanent,  31;  photomi- 
crographs of,  42,  43;  production 
of,  4,  20,  36;  protoplasm  and, 
60;  physical  reactions  of,  63;  sat- 
uration limit  in,  4,  26;  stability 
of,  4,  26,  29,  36,  38,  61;  types  of, 
3,  20,  41. 

Epitheliomas,  138. 

Ether,  7,  8,  10,  50,  52. 

Extraction  of  fat,  8. 

Extrusion  of  foreign  particles,  117. 


Fat,  extraction  of,  8;  in  hydrated 
colloids,  11,  29,  30;  deposition  of, 
19;  in  cells,  8,  57;  in  brain,  60; 
invisible,  10,  69;  visible,  10,  69; 
percentage  of,  in  tissues,  57  to  60; 
solvents,  50;  water  in,  12,  89; 
animal,  89. 

Fatty  degeneration,  8,  9,  11,  19,  20, 
67^  74,  75,  144;  definition  of,  67; 
nature  of,  67,  68;  in  protoplasm, 
68;  in  emulsions,  69;  history  of, 
81;  solution  theory  of,  84;  and 
lecithin,  85;  role  of  acids  in,  85; 
in  mammae,  106;  reversibility, 
144,  145. 

Fatty  infiltration,  9,  67,  68. 

Fatty  secretions,  8,  11,  89,  91,  95, 
138,  139. 

Fatty  tissues,  89,  90. 

Feel,  reaction  of  emulsions  to,  63. 

Fibrillar  structure,  123,  129. 

Fibromas,  131,  132. 

Figures,  inspissation,  133  to  138. 

Films,  interfacial,  28;  plasma,  64; 
waterproof,  139,  140. 

Finger  test,  32. 

Foams,  27. 

Foam  structure,  126. 

Foreign  particles,  extrusion  of,  117. 

Form,  maintenance  of,  7,  36. 


SUBJECT  INDEX 


153 


Formation  of  butter,  93,  94;  of 
connective  tissue,  130,  131,  132; 
of  new  organs,  132. 

Fruits,  139. 

Function,  altered,  143. 

G. 

Gall  Stones,   61. 
Gas  dispersions,  27. 
Gelatin^  6,  31,  33. 
Glands,  sebaceous,  95. 
Glue  test,  32. 
Granular  structure,  123. 
Growth,  14,  122. 

H. 

Heart  Disease,  76. 

Homogeneous   media,  separation  in, 

123. 
Homogenizer,  24. 
Honeycomb  structure,  123. 
History  of  Fatty  Degeneration,  81. 
Hyalin  structure,  101. 
Hydrated  colloids,  6,  21,  29,  30. 
Hydration  compounds,  21. 
Hydrophilic    colloids,    5;    hydration 

of,  7;    and  emulsifi cation,  34,  61; 

of  milk,  91. 


Importance  of  Emulsion  Chem- 
istry, 3,  15,  145. 

Infiltration,  fatty,  see  Fatty  Infil- 
tration. 

Inflammation,  143. 

Injury,  10,  143. 

Inspissation  figures,  133  to  138; 
circular,  138. 

Instructions  for  emulsification,  5,  29 
to  41. 

Interfacial  films,  28. 

Intoxication,  10;  by  acids,  10,  76. 

Invisible  fat,  10,  69. 

Involuntary  muscle  structure,  131, 
132. 

L. 
Lack  of  Oxygen,  76. 
Layers  in  breaking  emulsion,  39,  80. 


Lead,  10,  76. 

Leaves,  139. 

Lecithin  and  fatty  degeneration,  85. 

Linear  crackings,  133,  134. 

Lipoid  membranes,  30,  63,  64. 

Liquid  properties  of  protoplasm,  9, 

79. 
Living  matter,  118. 
Lung  structure,  126. 

M. 

Maintenance  of  Form,  7,  36. 

Making  of  emulsions,  19,  20,  25,  30, 
36;  of  butter,  12,  20,  93. 

Mammae,  cloudy  swelling  in,  106; 
fatty  degeneration  in,  106. 

Markings  of  skin,  133,  134. 

Matter,  living,  118;   non-living,  118. 

Mechanical  mixers,  22. 

Media,  separation  in  homogeneous, 
123. 

Membranes,  semipermeable,  9,  15; 
cell,  15,  63;  lipoid,  30,  63;  osmotic, 
63. 

Mercury,  10,  76. 

Metals,  poisoning  by,  9,  10,  76. 

Methods  of  emulsification,  5,  21,  22. 

Microscopic  appearance  of  emul- 
sions, 41,  42,  43. 

Milk,  13,  19,  20;  hydrophilic  col- 
loids in,  91;  and  butter  produc- 
tion, 93;  normal  production  of, 
105;  artificial  production  of,  108, 
109. 

Milks,  physical  reactions  of,  106. 

Mimicry  of  mucoid  secretion,  115;  of 
anatomical  structures,  121. 

Mineral  oils.  111. 

Mixers,  22. 

Motions,  surface,  117. 

Mucoid  secretion,  14;  mimicry  of, 
115;  model  of,  116. 

Myomas,  131,  132. 

N. 
Nature  of  Fatty  Degeneration, 

67,  68;  of  fatty  infiltration,  67. 
Necrosis,  144. 


154 


SUBJECT  INDEX 


Nerve,  9;  fat  in,  59,  60;  whiteness  of, 

62. 
New  organ  structure,  132. 
Non-living  matter,  118. 
Nuts,  91. 


(Edema,  143. 

Oil,  secretion  of,  19,  98,  138,  139; 
and  water  emulsions,  3,  21;  cot- 
tonseed, 4,  21,  25;  mineral,  111. 

Oily  secretions,  138,  139. 

Optical  changes  in  emulsions,  12,  96, 
98,  100. 

Organs,  fatty  degeneration  in  dead, 
84;    formation  of  new,  132. 

Osmic  acid,  62. 

Osmotic  concept,  9,  63. 

Osmotic  membranes,  9,  63. 

Oxygen,  lack  of,  76. 


Paper,  Reaction  of  Emulsions  to, 

63. 
Pearls,  138. 
Percentage  of  fat  in  tissues,  57  to  60; 

composition  of  bile,  62. 
Permanent  emulsions,  4,  31. 
Phase,  continuous,  21;    divided,  21; 

dispersed,  21.       , 
Phases,  distribution  between,  53. 
Phosphorus,  10,  76. 
Photomicrographs,  of  emulsions,  42, 

43;    of  fatty  degeneration,  69,  70, 

71. 
Plant  secretion,  96. 
Plants,  protective  coverings  of,    15, 

19,  138;  bloom  of,  139. 
Plasma  films,  64. 
Poisoning  by  metals,  74,  76. 
Post  mortem  fatty  degeneration,  84. 
Potassium  soap,  49. 
Prickle  cells,  129. 
Production    of    emulsions,     36;     of 

artificial  milk,  13,  108;   of  natural 

milk,  13,  105. 
Protective  coverings  of  plants,    15, 

19,  138. 


Protein,  61;  conversion  of,  into  fat, 
67. 

Protoplasm,  11;  structure  of,  15; 
as  an  emulsion,  60;  fatty  degen- 
eration of,  68;  fluidity  of,  79; 
solidity  of,  79. 

Protoplasmic  bridges,  127,  129. 

R. 

Reaction  to  Paper,  63;  to  feel,  63; 
of  butter,  94;  of  milk,  106;  to  in- 
jury, 10,  143;  inflammatory,  143. 

Reversibility  of  tissue  changes,  144, 
145. 

Rigidity  of  tissues,  76. 

Rods  and  cones,  128. 

Rubber,  20. 


S. 

Saccharose,  31. 

Sarcomas,  131,  132. 

Saturation  limit,  4,  26. 

Sebaceous  glands,  95. 

Sebum,  96. 

Secretions,  8;  of  colloid,  14,  115; 
mucoid,  14,  115,  116;  oily,  19,  98, 
138,  139;  fat  in,  57;  of  crystal- 
loids, 115;  fatty,  8,  11,  89,  91,  95, 
138,  139. 

Semipermeable  membranes,  9,  15. 

Separation  in  homogeneous  media, 
123. 

Skin  markings,  133,  134. 

Smegma,   96. 

Soap,  30,  31,  37,  61;  loss  of  hydro- 
philic  properties  of,  38;  calcium,  49; 
potassium,  49;  sodium,  49;  soft, 
50;  in  ear  wax,  96. 

Sodium  soap,  49. 

Soft  soap,  50. 

Softening  of  tissues,  9,  11,  76. 

Solid  properties  of  protoplasm,  9,  76. 

Solution  of  colloids,  32. 

Solution  theory  of  fatty  degenera- 
tion, 84. 

Solvents  for  fats,  50. 

StabiHzation,  4,  26,  29,  36,  38,  61. 


SUBJECT  INDEX 


155 


Starch,  31,  32,  51. 

Structure  in  protoplasm,  15,  123; 
hyalin,  101;  mimicry  of  anatom- 
ical, 121;  granular,  123;  honey- 
comb, 123;  of  foam,  126;  alveo- 
lar, 126;  of  lung,  128;  fibrillar, 
123,  129;  of  involuntary  muscle, 
131,  132. 

Subdivision  of  oil,  23,  24,  26. 

Sudan  III,  62. 

Sugar,  cane,  31. 

Surface  motions,  117. 

Surface  tension,  5,  27,  117. 

Swelling,  cloudy,  76,  143. 

Systems,  20. 


Tissues,  whiteness  of  nerve,  62;  sol- 
idity of,  9,  76;  fluidity  of,  9,  76; 
softening  of,   9,    11,   76;    adipose, 

11,  12,  89,  90;    water  in  adipose, 

12,  90;    fat  in,  57  to  60;    trans- 
parent, 101. 

Tropisms,  122. 

Tyndall  phenomenon,  44. 

Types  of  emulsions,  20,  41. 


Vascular  Disease,  76. 
Vemix  caseosa,  96. 
Viscosity,  7,  11,  27,  40,  76,  78. 
Visible  fat,  10,  40,  69. 


T. 

Tenacity,  6,  32. 
Tension,  surface,  5,  27,  ^17. 
Test,  glue,  32;  finger,  32. 
Theory,    solution,    of    fatty    degen- 
eration,   84. 
Third  phase,  28. 
Thrombosis,  76. 
Tissue  changes,  reversal  of,  144. 


W. 
Waller's  Degeneration,  76. 
Water-in-fat    emulsions,    3,    21,  41; 

fatty  tissues  as,  90. 
Water  in  fat,    12,   89;     in  adipose 

tissues,  12,  90. 
Waterproof  films,  139,  140. 
Whiteness  of  nerve  tissue,  62. 
Whorls.  138. 


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